topics for stem cell research

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Stem-cell research articles from across Nature Portfolio

Stem-cell research is the area of research that studies the properties of stem cells and their potential use in medicine. As stem cells are the source of all tissues, understanding their properties helps in our understanding of the healthy and diseased body's development and homeostasis.

Latest Research and Reviews

Genome engineering with Cas9 and AAV repair templates generates frequent concatemeric insertions of viral vectors

AAV vectors form difficult-to-detect concatemers at Cas9 target sites.

• Fabian P. Suchy
• Daiki Karigane
• Hiromitsu Nakauchi

A two-way street – cellular metabolism and myofibroblast contraction

• Birgit Sawitzki
• Georg N. Duda

Comparison studies identify mesenchymal stromal cells with potent regenerative activity in osteoarthritis treatment

• Hongshang Chu
• Shaoyang Zhang

ATG or post-transplant cyclophosphamide to prevent GVHD in matched unrelated stem cell transplantation?

• Olaf Penack
• Mouad Abouqateb
• Zinaida Peric

Depleting myeloid-biased haematopoietic stem cells rejuvenates aged immunity

Antibody-mediated depletion of myeloid-biased haematopoietic stem cells in aged mice restores characteristic features of a more youthful immune system.

• Jason B. Ross
• Lara M. Myers
• Irving L. Weissman

Generating human bone marrow organoids for disease modeling and drug discovery

This protocol can be used to generate three-dimensional vascularized bone marrow organoids from human induced pluripotent stem cells. The organoids contain key stromal and hematopoietic cell types and can be engrafted with normal and malignant cells from adult donors to model niche interactions.

• Aude-Anais Olijnik
• Antonio Rodriguez-Romera
• Abdullah O. Khan

News and Comment

Improving the EASIX’ predictive power for NRM in adults undergoing allogeneic hematopoietic cell transplantation

• Silvia Escribano-Serrat
• Luis Gerardo Rodríguez-Lobato
• María Queralt Salas

Minimally invasive derivation of primary human epithelial organoids from fetal fluids

Primary fetal organoids are currently derived from tissue samples obtained at termination of pregnancy. We developed an approach that enables prenatal derivation of epithelial organoids from fetal fluids. Single-cell mapping of the human amniotic fluid content unveiled the presence of viable fetal epithelial progenitors of multiple tissues that can form fetal lung, kidney and intestinal organoids.

How to decrease bone marrow collection volume and risk contaminations via the operating room cell concentration?

• Yoann Grimaud
• Flore Sicre de Fontbrune
• Lionel Faivre

Early lymphocyte reconstitution and viral infections in adolescents and adults transplanted for sickle cell disease

• Loïc Vasseur
• Alexis Cuffel
• Nathalie Dhédin

Post-transplant cyclophosphamide with Sirolimus or Cyclosporine for GvHD prophylaxis in matched related and unrelated transplantation: a two-center analysis on 213 consecutive patients

• Simona Piemontese
• Maria Teresa Lupo Stanghellini
• Patrizia Chiusolo

Donor NKG2D rs1049174 polymorphism predicts hematopoietic recovery and event-free survival after single-unit cord blood transplantation in adults

• Takaaki Konuma
• Megumi Hamatani-Asakura
• Satoshi Takahashi

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The cover of this issue of Emerging Topics in Life Sciences (volume 5, issue 4) features a fl owchart from Hulme et al. showing the sources and characteristics of multipotent mesenchymal stromal cells (MSCs). Read more about the Current Topics in Stem Cells and Regenerative Medicine in this special issue.

Competing Interests

Abbreviations, current topics in stem cell biology and regenerative medicine: a regional perspective from the united kingdom.

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William Eustace Johnson; Current topics in stem cell biology and regenerative medicine: a regional perspective from the United Kingdom. Emerg Top Life Sci 29 October 2021; 5 (4): 495–496. doi: https://doi.org/10.1042/ETLS20210264

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• Ris (Zotero)
• Reference Manager

This special issue of Emerging Topics in Life Sciences entitled ‘Current Topics in Stem Cells and Regenerative Medicine’ brings together expertise from a collaborative organisation known as the Mercia Stem Cell Alliance (MSCA). The alliance was established initially by Professors Sue Kimber (University of Manchester) and Jon Frampton (University of Birmingham) just over 10 years ago and now has multiple regional centres of excellence across the Midlands and North West of the UK, including Aston University, University of Chester, Keele University, Manchester Metropolitan University, Lancaster University, University of Leicester, University of Liverpool, Liverpool John Moore's University, Loughborough University, University of Nottingham, University of Oxford, University of Sheffield, University of York. Many of these centres have contributed reviews to this issue. The MSCA also partners with industrial and clinical organisations, including the NHS, and is active in bringing stem cells and regenerative medicines to a meaningful translational endpoint (see: http://www.msca.manchester.ac.uk/ ).

The reviews published in the special issue cover key areas in stem cell biology and regenerative medicine, from aspects of basic stem cell research through to the use of stem cells and tissue engineering to model human pathophysiology and for drug development through to clinical applications of adult stem cells and other regenerative medicines. Dogan and Forsyth (Keele University) have reported how epigenetic mechanisms influence telomerase activity, which plays an essential, although not fully understood role in regulating pluripotent stem cell proliferation, differentiation, tissue repair and cancer [ 1 ]. Walczak et al. [ 2 ] (Aston University) have examined the use of induced pluripotent stem cells and advanced tissue engineering to enable in vitro generation of 3D tissue culture models that match the complexity of the human CNS. The concept of using cell spray technologies to deliver stem cells to the CNS in the treatment of neurological trauma and pathology, e.g. following spinal cord injury, has been described and discussed by Chari and co-workers (Keele University) [ 3 ]. The use of bio-derived materials as wound dressings to promote skin wound repair has been reviewed by Verdolino et al. [ 4 ] (University of Manchester), who also consider how such products have been developed to help overcome inflammatory issues that lead to chronic wounds. There are two complimentary reviews on mesenchymal stem/stromal cells (MSCs). Kuntin and Genever (University of York) have provided an informative historical overview of MSC biology, including MSC differentiation potential and secretome activity, detailing issues of MSC heterogeneity, and calling for further basic research to better understand their mechanisms of action [ 5 ]. The need to better understand how MSCs may work as regenerative medicines has been revisited by Amadeo et al. [ 6 ] (University of Liverpool), who further critique the application of MSCs in animal disease models, which has contributed to what seems like a confusing picture in terms of determining predictive outcomes for clinical trials in humans. Stewart (Liverpool John Moore's University) has considered the use of adult stem cells and other regenerative medicines, including platelet rich plasma, specifically in the sporting arena. This review demonstrates the potential of stem cells and regenerative medicines to help alleviate human suffering as well as offset financial burdens associated with the treatment costs for traumatic injuries, but also discusses the use of stem cells to enhance sporting performance [ 7 ]. Finally, Hulme et al. [ 8 ] (RJAH Orthopaedic Hospital/Keele University) review the current state of the art for the use of cell transplants for cartilage repair, which has been a pioneering exemplar in the field of regenerative medicine for musculoskeletal pathology.

We are grateful to Emerging Topics in Life Sciences and Portland Press for inviting the reviews, which have been written in such a manner that they are broad in outlook, whilst deep in content. One of the main objectives of the MSCA is to help basic researchers and translational scientists learn and work together, both to increase our fundamental understanding of the molecular and cell biology that underpins this exciting field and also to successfully develop new stem cell therapies. Hence, it is hoped that the special issue will provide a useful resource to many current and next generation investigators as they progress in their careers in stem cell research.

The author declares that there are no competing interests associated with this manuscript.

This manuscript was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC).

Mercia Stem Cell Alliance

mesenchymal stem/stromal cells

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Focus On Stem Cell Research

Stem cells possess the unique ability to differentiate into many distinct cell types in the body, including brain cells, but they also retain the ability to produce more stem cells, a process termed self-renewal. There are multiple types of stem cell, such as embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, and adult or somatic stem cells. While various types of stem cells share similar properties there are differences as well. For example, ES cells and iPS cells are able to differentiate into any type of cell, whereas adult stem cells are more restricted in their potential. The promise of all stem cells for use in future therapies is exciting, but significant technical hurdles remain that will only be overcome through years of intensive research.

NINDS supports a diverse array of research on stem cells, from studies of the basic biology of stem cells in the developing and adult mammalian brain, to studies focusing on nervous system disorders such as ALS or spinal cord injury. Other examples of NINDS funded research include using iPS cells to derive dopamine-producing neurons that might alleviate symptoms in patients with Parkinson’s disease, and using ES cells to generate cerebral organoids to model Zika virus infection.

Estimates of Funding for Various Research, Condition, and Disease Categories

Resources and tools.

Timothy LaVaute, Ph.D. | Program Director, Repair and Plasticity  [email protected]

Funding Opportunities 

NIH Common Fund Somatic Cell Genome Editing Letters of intent are due April 4, 2018

Search the NIH Guide to Grants and Contracts . Use key words such as “neurological disease” and “stem cell” or “regenerative medicine” in your search.

News & Events

CRISPR helps find new genetic suspects behind ALS/FTD

Memory gene goes viral

Study suggests lasting benefits of cord blood transplants in infants with Krabbe disease

Related Topics  NIH Stem Cell Information Page NIH Policies related to stem cell research NINDS Human Cell and Data Repository NEUROLINCS NIH Human Embryonic Stem Cell Registry NINDS Repository at the Coriell Institute for Medical Research Regenerative Medicine Program (RMP) Regenerative Medicine Innovative Project (RMIP)

Articles on Stem cell research

Displaying 1 - 20 of 48 articles.

Triggering cancer cells to become normal cells – how stem cell therapies can provide new ways to stop tumors from spreading or growing back

Huanhuan Joyce Chen , University of Chicago Pritzker School of Molecular Engineering and Abhimanyu Thakur , University of Chicago Pritzker School of Molecular Engineering

Limits for human embryo research have been changed: this calls for public debate

Sheetal Soni , University of KwaZulu-Natal

New global guidelines for stem cell research aim to drive discussions, not lay down the law

Megan Munsie , The University of Melbourne and Melissa Little , Murdoch Children's Research Institute

The key to treating multiple sclerosis could be inside sufferers’ own bodies

Chris McMurran , University of Cambridge

First working eggs made from stem cells points to fertility breakthrough

Adam Watkins , Aston University

New autism research: a nutrient called carnitine might counteract gene mutations linked with ASD risks

Vytas A. Bankaitis , Texas A&M University and Zhigang Xie , Texas A&M University

Informed consent for stem cell research: why it matters and what you should know

Leslie Jacqueline Greenberg , University of Cape Town

How to make sure South Africa’s biobanks balance scientific progress with the law

Ames Dhai , University of the Witwatersrand and Safia Mahomed , University of the Witwatersrand

South Africa’s struggle to control sham stem cell treatments

Melodie Labuschaigne , University of South Africa and Michael Sean Pepper , University of Pretoria

Why the world needs to keep pace with breakthroughs in stem cell research

Marietjie Botes , University of Pretoria and Marco Alessandrini , University of Pretoria

Why South Africa needs better laws for stem cell research and therapy

Michael Sean Pepper , University of Pretoria ; Janine Scholefield , Council for Scientific and Industrial Research ; Melodie Labuschaigne , University of South Africa , and Robea Ballo , University of Cape Town

What lies behind the hype and the hope of stem cell research and therapy

Michael Sean Pepper , University of Pretoria and Nicolas Novitzky , University of Cape Town

A beginner’s guide to understanding stem cells

Michael Sean Pepper , University of Pretoria

Curing baldness may just be about having enough pluck

Cheng-Ming Chuong , University of Southern California

‘One of Us’ petition marks a sinister mobilisation of the pro-life movement in Europe

Sheelagh McGuinness , University of Birmingham and Heather Widdows , University of Birmingham

BAMI trial might provide bone marrow answers, but it won’t teach us much about stem cells

Jalees Rehman , University of Illinois Chicago

Opinions about scientific advances blur party-political lines

Matthew C. Nisbet , American University and Ezra Markowitz , Columbia University

Stem cells offer a more natural approach to plastic surgery

Ash Mosahebi , UCL

Biowire technology brings stem cells to life in human heart

University of Toronto

Dream of regenerating human body parts gets a little closer

James Godwin , Monash University

Related Topics

• African stem cells
• Clinical trials
• Embryonic stem cells
• Medical research
• Organ transplantation
• Stem cell therapy

Top contributors

Director, Institute for Cellular and Molecular Medicine & SAMRC Extramural Unit for Stem Cell Research & Therapy, University of Pretoria

Professor and Former Program Leader of Stem Cells Australia, The University of Melbourne

Professor of Law, College of Law, University of South Africa

Professor and Director, Centre for Genetic Diseases, Monash Institute of Medical Research, Monash University

Research Group Leader, Stem Cells, CSIRO

Deputy Vice-Chancellor Academic Quality and Professor of Molecular Biology, UNSW Sydney

Head of Neural Transplantation, Florey Institute of Neuroscience and Mental Health

Law lecturer & doctoral student, University of Sydney

Post-doctoral research fellow at the Queensland Brain Institute, The University of Queensland

PhD Scholar, Monash Institute of Medical Research, Monash University

Laboratory
 Head,
 Monash 
Institute 
for
 Medical
 Research, Monash University

Co-director of the Immunology Research Centre, St Vincent's Hospital Melbourne

Post-doctoral researcher in Stem Cell biology and Human Nutrition, The University of Western Australia

Professor in Clinical Ethics, Macquarie University

Professor and Director of the Colgate Australian Clinical Dental Research Centre, University of Adelaide

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75 Stem Cell Essay Topic Ideas & Examples

🏆 best stem cell topic ideas & essay examples, ⭐ good research topics about stem cell, 👍 simple & easy stem cell essay titles.

• Stem Cell Research D, in the article I am Pro-Life and Oppose Embryonic Stem Cell Research, opposes stem cell research in particular embryonic stem cell research.
• Stem Cell Treatment, Its Benefits and Efficiency Stem cell treatment is a method that uses the transplantation of cells to facilitate the process of cell regeneration. In conclusion, stem cell therapy is expected to provide a breakthrough in the treatment of adverse […] We will write a custom essay specifically for you by our professional experts 808 writers online Learn More
• The Issue of Stem Cells One of the common misconceptions is that stem cells research violates ethical principles since it uses embryonic stem cells or the so-called fetus.
• Ethical Aspects of Stem Cell Research Firstly, the leading argument against the use of stem cell-based therapy is the fact that it leads to the destruction of a human embryo.
• Neural Stem Cells in Therapeutic Purposes Neural stems cells must be used as a therapeutic measure to slow or halt the aging process due to their rejuvenation and differentiation capabilities.
• Applying Neural Stem Cells to Counteract Brain Aging Pluripotent stem cells, or PSCs, are the best candidates for in vitro generation and cultivation of neural stem cells. Neural stem cells: Origin, heterogeneity and regulation in the adult mammalian brain.
• Stem Cells Applications in Bone and Tooth Repair and Regeneration It provides examples of scientific research about the application of stem cells in the process of the regeneration of bones and teeth.
• Ethical and Safety Issues of Stem Cell-Based Therapy Ilic and Ogilvie argue that this is a dilemma between the obligation of doctors and scientists to save lives and the need to destroy it in order to obtain stem cells.
• Blood Stem Cell Self-Renewal and Differentiation One of the distinct cells in the blood or hematopoietic stem cell. Due to this functionality, the blood and skin cells’ pose the greatest ability of differentiation and self-renewal.
• Embryonic Stem Cells and Nuclear Transfer Somatic cell dedifferentiation is the “direct reprogramming of an adult somatic cell to return to the state of a pluripotent stem cell” The pros of nuclear transfer are that these embryonic stem cells, which contain […]
• Stem Cell Regenerative Therapy This method is well-studied and has a proven track record of improving spinal stenosis, unlike stem cells. This evidence suggests that stem cells can potentially reverse the degeneration of bone and tissue.
• “What’s the Fuss about Stem Cells?” The primary goal of this essay is to emphasize the importance of the research of the stem cells, provide a precise definition, and explain their functions in the body.
• The Stem Cell Research: Key Aspects In light of the legal aspects of the research, the paper indicates that the human embryo deserves respect just as adults.
• Apple Stem Cell in Skincare Researchers have shown that extracts from Swiss apple, Malus domestica, have regenerative effect on skin, and thus have utilized them in the production of apple stem cells from adult cells.
• Ethical Debate of Stem Cell Research The authors of the article Cogle et al.researched under the auspices of Stem Cell Biology and Regenerative Medicine Program of the University of Florida Shands Cancer Center.
• Stem Cell Research: Some Pros and Cons The science of stem cell treatments, potentially as or more significant than these other innovations, is beginning a new stage of exploration and growth that could be the forerunner of unprecedented cures and therapies.
• Stem Cells Biology: Features and Researchs Stem cells are cells that have the capacity to subdivide into other cells. The second property of stem cells is that they can develop into specialized cells in the differentiation process.
• Nanoscale Silver and Stem Cell Research Whether nanoscale silver or stem cell research, patients realize that the benefits of this technology go without saying. While silver provides many effective applications, stem cell research is the best alternative for curing pancreatic cancer.
• Stem Cell Research from Catholic Perspective The argument exists that because some embryos are created in petri dishes and require implantation into a womb to achieve their full potential that they should not be considered human life, and therefore, can be […]
• Ethics of Stem Cell Research Creating Superhumans Stem cell research is a subject that has generally been absent from the current public and political debates, pushed to the backburner by issues such as the economy, the Iraq War, healthcare, and immigration.
• Stem Cells Therapy of Rheumatoid Arthritis As such, research into the application of the method to the treatment of various conditions is crucial. According to Lillis, the condition causes an inflammation that can extend to the cartilage as well as other […]
• Embryonic Cells in Stem Cell Research Therefore, despite possible ethical concerns associated with the implications of SCR on human nature, I believe that the use of embryonic cells as one of the key aspects of CSR should be promoted as a […]
• Stem Cell Therapies Evaluation The author of this article is Zara Jethani, and she argues that neuroscience is one of the priorities in modern medicine, and this approach to treatment may allow restructuring damaged tissues and cells.
• A Promising Prognosis in Stem Cell Therapy The investigation of adult stem cells and induced pluripotent stem cells is of increasing interest as these cells have the most potential for the restoration of myocardial infarction-induced tissue damages.
• Stem Cell Therapy as a Potential Cure for Diabetes The results of a specialized study by Chhabra and Brayman on the treatment of diabetes type 2, which makes 90% to 95% of the cases known globally, has shown that it is viable to treat […]
• Stem Cell Therapy and Diabetes Medical Research This type of diabetes is less common and only occurs during the early stage when the immune system of the body attacks and destroys cells that produce insulin in the pancreas.
• The Controversy Surrounding Adult Stem Cell Research The main fear exposed in the video was that the use of stem cells to treat a disease may result in the seeding of cancer throughout the body.
• Stem Cell Therapy in Colorectal Cancer The novel therapeutic methods used against colorectal cancer stem cells ranges from antibodies and antibody constructs to engineered nanoparticles that target cancerous stem cells in the colon.
• Factors That Influence Stem Cell Research For instance, the GDP of the United States measures the value of goods and services produced within the boundaries of the United States, by people living in the U.S.even if they are not American citizens. […]
• Using Embryonic Stem Cells to Grow Body Parts The use of embryonic stem cells is one of the important medical innovations of the 21st century. The process entails disassembling the embryo to get stem cells that are located in the internal parts of […]
• Kant’s Moral Philosophy on Stem Cell Research In Kant’s own words, “Autonomy of the will is the property that the will has of being a law to itself.[Morality] is the relation of actions to the autonomy of the will […].
• The Research and Use of Stem Cell Embryos Policies of governments across the globe vary on the legality of the prohibited and allowed research and use of stem cell embryos.
• Neural Stem Cells, Viral Vectors in Gene Therapy and Restriction Enzymes The nervous system is comprised of specialized type of cells called Neural Stem Cells. Developmental versatility of plasticity of neural stem cells is important in formation of these different neural cells.
• Stem Cell Research Implementation Nevertheless, the lack of adequate funding from the government has deteriorated the efforts of the researchers in embracing the benefits of this technology.
• Expanding Federal Government Funding of Stem Cell Research This is because stem cell research promises to cure degenerative diseases such as Alzheimer’s and scoliosis but the same time the cure requires the destruction of human embryonic stem cells that can only be had […]
• Adipose-Derived Mesenchymal Stem Cell Application Combined With Fibrin Matrix
• Embryonic Stem Cell Research Provides Revolutionary and Life-Saving Breakthroughs
• Immune Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation
• Ethical and Beneficial Replacement for Embryonic Stem Cell Research
• Biopsy Needle Advancement During Bone Marrow Aspiration and Mesenchymal Stem Cell Concentration
• Autoimmunity Following Allogeneic Hematopoietic Stem Cell Transplantation
• Bioinformatics Analysis and Biomarkers With Cancer Stem Cell Characteristics in Lung Squamous Cell Carcinoma
• Induced Pluripotent Stem Cell-Based Cancer Vaccines
• Embryonic Stem Cell Research: A New Paradigm in Medical Technology
• Advanced Functional Biomaterials for Stem Cell Delivery in Regenerative Engineering and Medicine
• Pragmatic Pluralism: Mutual Tolerance of Contested Understandings Between Orthodox and Alternative Practitioners in Autologous Stem Cell Transplantation
• Allogeneic Hematopoietic Stem Cell Transplantation in a Rare Case of Tonsillar Mast Cell Sarcoma
• Stem Cell Fate Determination During Development and Regeneration of Ectodermal Organs
• Biomimetic Extracellular Matrix Mediated Somatic Stem Cell Differentiation: Applications in Dental Pulp Tissue Regeneration
• Adult Stem Cell and Mesenchymal Progenitor Theories of Aging
• Ethical, Legal, and Social Issues in Genome or Stem Cell Research
• Defective Pulmonary Innate Immune Responses Post-stem Cell Transplantation
• Stem Cell Therapy for Diabetes
• Embryonic Stem Cell Research: The Pandora’s Box of Science
• Bone Marrow Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
• Human Organ Culture: Updating the Approach to Bridge the Gap From in Vitro to in Vivo in Inflammation, Cancer, and Stem Cell Biology
• Adult Stem Cell Therapies for Wound Healing: Biomaterials and Computational Models
• Evaluating the Endocytosis and Lineage-Specification Properties of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Targeted Therapeutic Applications
• Hematopoietic Stem Cell Transcription Factors in Cardiovascular Pathology
• Central Nervous System Complications in Children Receiving Chemotherapy or Hematopoietic Stem Cell Transplantation
• Christian Ethics and Embryonic Stem Cell Research
• Funding Stem Cell Research: A New Field of Innovative Medicine
• Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging
• Stem Cell Research and Its Effects on the Future of Medicine
• Developing Stem Cell-Based Therapies for Neural Repair
• Bioethical and Political Debates Surrounding Embryonic Stem Cell Research
• Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis
• Mitochondrial Medicine: Genetic Underpinnings and Disease Modeling Using Induced Pluripotent Stem Cell Technology
• Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement
• Embryonic Stem Cell Research Could Help Out Many People
• Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via Akt Activation
• Human Liver Stem Cell-Derived Extracellular Vesicles Prevent Aristolochic Acid-Induced Kidney Fibrosis
• Stem Cell Therapy for Pediatric Traumatic Brain Injury
• Continuous Immune Cell Differentiation Inferred From Single-Cell Measurements Following Allogeneic Stem Cell Transplantation
• Stem Cell-Friendly Scaffold Biomaterials: Applications for Bone Tissue Engineering and Regenerative Medicine
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100 Stem Cell Research Topics + Examples

Are you looking for stem cell research topics? StudyCorgi has compiled a list of stem cell topics suitable for a research paper, essay, presentation, thesis, and other assignments. Our proposed titles go beyond examining the pros and cons of stem cell research and therapy and provide many fresh insights on this subject. We hope that our list will give you inspiration for developing your own project ideas.

🏆 Best Stem Cell Research Topics

🔎 easy stem cell research paper topics, 🎓 most interesting stem cell research paper topics, 💡 simple stem cell research topics for research paper, ❓ stem cell research questions.

• Advantages and Disadvantages of Stem Cell Research
• Stem Cell Research Essay: Research Ethics, Pros and Cons, and Benefits
• Stem Cell Research: Ethical Nursing Principle
• Stem Cell Debate: Advantages and Disadvantages of Stem Cell Technology
• Pros and Cons of Stem Cell Research
• Brainstorm: Stem Cells Research
• Stem Cell Research Justification and Benefits
• Ethical Issues in Stem Cell Research This essay describes the ethical issues in the field, human protection, and informed consent. A background to stem cell research will also be presented.
• Theories of Aging and Stem Cell Aging Aging is associated with the reduction in the force of natural selection as it relates to a mutation that generates negative effects in the later stage of life.
• Sources Credibility in Internet Information About Stem Cells Research The standards for identifying a valid source about stem cell research are website layout, details of the topic’s explanation, references to scientific papers, etc.
• Bio Ethics and Stem Cell Research The advancement in technology and science has helped man over the years to come up with miraculous cures and inventions; profitable to mankind in all ways possible.
• Stem Cell: Environmental Science Stem cells are the type of cells that are really able to distinguish into types of cells, but they as well maintain the ability to renew all the way through the cell division.
• Stem Cells and Related Ethical Controversy The controversy of stem cells arises from the fact that a human embryo has to be destroyed to extract the stem cell.
• Ethical and Legal Regulation of Human Tissues and Stem Cells Research in the European Union Major advances in biological sciences have yielded new ways of tackling various environmental and health problems.
• Stem Cell Research as Ethical Health Care Issue In stem cell research, respect for autonomy involves the relationship between scientific research and the public through an emphasis on the importance of research.
• Stem Cells Research for the Cure of Cerebral Palsy The use of stem cells to cure cerebral palsy involves the introduction of the cells to the affected brain region so that they could grow and enable the part of the brain.
• Debate on Stem Cell Development from Human Embryo Several ethical debates have been conducted in the past concerning the development, utilization, and obliteration of human embryos.
• Stem Cells: Definition and Research Articles’ Analysis The purpose of this report is to define stem cells and assess the research on stem cells by analyzing and summarizing six scholarly articles.
• Use of Adult Stem Cells in Medicine The use of adult stem cells can lead to severe unintended outcomes which might compromise their application and acceptance.
• Stem Cell Therapy in the Treatment of Heart Disease Stem cell therapy is a viable strategy in treating heart disease, but it is still undergoing research; therefore, healthcare professionals should be cautious in pursuing it as a treatment option.
• Embryonic Stem Cell Research and Government Funding This paper discusses the values of embryonic stem cell research and whether it is appropriate for the government to finance it.
• Human Embryonic Stem Cell Research In the world of bioethics the discussion on human embryonic stem cell research has resulted in a heated debate, from Washington D.C. and to the other parts of the United States of America.
• Fetal Rights vs. Stem Cell Research The rise of genetics as a scientific discipline had proven that the answers to social, political, and cultural problems lay exclusively in the field of biology.
• Stem Cell Research. Fetal Rights vs. Science The concept of the scientific study of the next stage of development, the fetus, which resulted from abortion, is unthinkable and unethical.
• California Is Crazy About Stem Cells The research on stem cells and their use in treating different conditions as well as associated debates have become very popular during recent years.
• Implementing Cost-Effective Stem Cell Innovation The purpose of the paper is to explore the broader issues that impact clinical trials of stem cell research and treatment in general.
• Adipose Stem Cells for Tissue Regeneration “Adipose stem cells: Biology and clinical applications for tissue repair and regeneration” describes the whole process of recovery in detail.
• Human Adult Versus Embryonic Stem Cells Study The controversies of human stem cell research and therapy has led to many governments taking considerable legislative actions that would severely regulate the field.
• Adult Stem Cell Research, Its Present and Future This analytical treatise attempts to explicitly review the controversies surrounding stem cell research to understand its current position in society.
• Bio Ethics and Stem Cell Research Stem Cell Research, when started, sprung with controversies since the start as it proved to be unethical when seen through the religious perspective.
• Alzheimer’s Disease and Stem Cell Research
• Cancer Stem Cell Metabolism and Potential Therapeutic Targets
• Stem Cell Research and Neurodegenerative Diseases
• The Apgar and Stem Cell Research
• Cancer Stem Cell Hierarchy in Glioblastoma Multiforme
• Myths About Embryonic Stem Cell Research
• Stem Cell Therapy: Medico-Legal Perspectives in Italy
• Neural Stem Cell Regulation by Adhesion Molecules Within the Subependymal Niche
• Stem Cell Therapy for Diabetes
• Hepatocellular Carcinoma: From Hepatocyte to Liver Cancer Stem Cell
• Stem Cell Research and the Catholic Church
• Agents That Inhibit Stem Cell-Resistant Chemotherapy
• The Stem Cell State in Plant Development and Response to Stress
• Stem Cell Donor Matching for Patients of Mixed Race
• Arguing for Embryonic Stem Cell Research
• MiRNAs Regulate Stem Cell Self-Renewal and Differentiation
• Stem Cell Therapy for Heart Failure
• The Extraocular Muscle Stem Cell Niche Is Resistant to Ageing and Disease
• Embryonic Stem Cell-Like Subpopulations in Venous Malformation
• Stem Cell Origin Differently Affects Bone Tissue Engineering Strategies
• Neural Stem Cell Niche and Egfr Protein
• Stem Cell-Derived Extracellular Vesicles and Immune-Modulation
• Miracles and Tragedies With Stem Cell Treatment
• Sustained Delivery System for Stem Cell-Derived Exosomes
• Stem Cell Research and Its Effects on the Future of Medicine
• The Stem Cell Connection of Pituitary Tumors
• Reproductive Human Stem Cell Cloning
• Stem Cell Activity Towards Tissue Regeneration
• The Signaling Pathways That Control Stem Cell Fate
• Drug Discovery via Human-Derived Stem Cell Organoids
• Therapeutic Cloning and Stem Cell Therapy in South Korea
• The Stem Cell Debate Is Not About Medical Benefits
• Embryonic Stem Cell Research Ethical or Unethical
• Genetic Engineering, Cloning, and Stem Cell Research
• Sickle Cell and the Promise of Stem Cell Therapy
• Mesenchymal Stem Cell Therapy for Aging Frailty
• Christian Ethics and Embryonic Stem Cell Research
• Biotechnology and Stem Cell Research
• Developing Stem Cell-Based Therapies for Neural Repair
• Stem Cell Treatment for Spinal Cord Injuries
• How Do Stem Cells Act as Biorepair Kits?
• How Can Stem Cells Be Used to Treat Human Diseases?
• What Type of Stem Cells Are Isolated From the Inner Mass of Pre-implantation Embryos?
• What Are the Potential Dangers of Stem Cell Technology?
• Why Is Stem Cell Research Controversial?
• Why Is Stem Cell Research Not Allowed Fully in the United States?
• What Is Stem Cell Theory?
• What Are the Arguments in Favor of Stem Cell Therapy?
• What Are Some Applications for Stem Cells?
• What Is the Importance of Stem Cell Transplantation?
• How Do Stem Cells Differentiate?
• Is Stem Cell Therapy the Same as a Bone Marrow Transplant?
• Which Stem Cell Differentiates to Form Neutrophils?
• What Is Somatic Stem Cell Therapy?
• How Do Researchers Turn Stem Cells Into Different Types of Cells in a Laboratory?
• What Do Stem Cells in Your Bone Marrow Eventually Become?
• What Happens When Stem Cells Receive Their Signal?
• Are Somatic Stem Cells Pluripotent?
• What Does It Take To Keep a Stem Cell Alive in the Lab?
• How Do Adult Stem Cells Differ From Pluripotent Stem Cells?
• Why Did the Bush Administration Deny Stem Cell Research?
• Is Animal Stem Cell Research Ethical?
• How Is Stem Cell Research Similar to Developmental Biology?
• Where Do Adult Somatic Stem Cells Originate?
• Which Type of Stem Cell Gives Rise to Red and White Blood Cells?
• Should Stem Cell Research Be Legal?
• What Would Happen if Human Doesn’t Have Stem Cells?
• What Is Using Stem Cells to Produce Healthy Tissues to Treat Degenerative Diseases Called?
• What Is the Difference Between the Different Kinds of Stem Cells?
• What Part of a Human Bone Contains Stem Cells?

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Topics: Stem Cell Research

A guide that provides information and resources on teaching responsible conduct of research that focuses on the topic of stem cell research. Part of the Resources for Research Ethics Education collection.

What is Research Ethics

Why Teach Research Ethics

Animal Subjects

Biosecurity

Collaboration

Conflicts of Interest

Data Management

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Social Responsibility

Stem Cell Research

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• Critically evaluate the decision to conduct research with stem cells Both the spirit of the regulations and good science requires that individuals give thoughtful consideration to what defines an acceptable use of stem cells.  
• Comply with regulations Having made a considered decision to use human stem cells, no use of those cells for the purposes of research, teaching, or testing should commence that is not explicitly part of an approved protocol or specifically waived under relevant regulations.  
• Promote responsible use of stem cells If you are responsible for training others or if you observe indifference to considerations for responsible stem cell research, you should make attempts to initiate discussion, identify relevant regulations, and promote responsibility. If significant violations of regulations are observed, then those observations should be reported to the appropriate people in the institution.

In recent years, biomedical research has been significantly altered by technologies for the derivation of human cell lines capable of differentiation into any of the cells of the human body. Such cells are sometimes called "pluripotent" because they have the power ("potency") to become many ("pluri-") different cells. It has long been known that such cells exist, but it wasn’t until 1981 that stem cells were isolated from mouse embryos (Evans and Kaufman, 1981; Martin, 1981), and only in 1998 that the derivation of human embryonic stem cells was first reported (Thomson et al., 1998). This tool was quickly recognized as an opportunity to better understand normal and pathological human development, to identify and test new pharmacological therapies, and perhaps to even replace diseased tissues or organs. Many scientists viewed this as a potentially revolutionary approach to studying human biology. However, because a necessary first step was to use and destroy human embryos such research raised serious questions for some members of the public, as well as some scientists.

While most hESC scientists view the human embryo as human cells with great biological and scientific potential, there are many members of our society who hold religious beliefs that define the human embryo as equivalent to a human life. By this view, any harm or destruction of the human embryo is tantamount to harm or destruction of a human life. This perspective has become more than a matter of personal opinion. For many years now, under the Dickey amendment (1995), the U.S. Congress has agreed to federal restrictions on any research that would require harm or destruction of the human embryo. This restriction was partially lifted in 2001 by President Bush’s announcement that research with stem cell lines existing as of August 9, 2001, could be eligible for federal funding.

Subsequently, President Obama announced a new approach to approving stem cell lines for federal funding (Obama, 2009). The question now is not whether stem cell lines were created before a particular date, but whether or not those lines meet criteria that have been defined for ethically derived stem cell lines (NIH, 2009). While the result has been an increase in the number of stem cell lines approved for federal funding, it is noteworthy that the number of lines meeting these criteria is limited (NIH Human Embryonic Stem Cell Registry). In fact, many of the lines approved under the Bush policy are not acceptable under the Obama guidelines.

It would be a mistake to assume that religion is the only basis for arguments against hESC research. It is clear that some individuals and groups are motivated more by philosophical, political, or even economic arguments. However, whether based on religion or otherwise, most polls show that opponents to hESC research may represent a minority, but that minority is substantial in size and in impact (e.g., pollingreport.com).

Stem cells can be obtained from embryos, but embryos are only one of many potential sources. In the fetus, and even in an adult, stem cells can be found in many body tissues. The best known of these sources is bone marrow, in which stem cells are produced that are capable of differentiating into different types of blood cells. However, these stem cells are not pluripotent as defined above. Such cells are often called adult or tissue-specific stem cells. These cells have important, but restricted, clinical applications distinct from the wider range of possibilities with human embryonic stem cells (Wood, 2005).

Several sources of pluripotent stem cells have now been identified. One of these sources is based on the technology used to clone “Dolly” the sheep (Campbell et al., 1996), “Snuppy” the dog (Lee et al., 2005), and many other mammalian species. The first step to cloning these animals is a technique called Somatic Cell Nuclear Transfer (SCNT). SCNT in any species begins with an egg of that species from which the genetic material is removed. This egg can then be fused with an adult cell of the individual to be cloned. The result is an egg that now contains a full complement of DNA. Under appropriate laboratory conditions, that egg can be induced to divide as if it were a fertilized egg. If allowed to progress far enough, the resulting embryo can be implanted in the uterus of an individual of the same species, potentially resulting in the birth of a clone. However, it is also possible to allow the “embryo” to develop only for the purpose of harvesting stem cells rather than implantation. This source of stem cells is particularly important for stem cell research as well as potential therapies because of the opportunity to produce stem cells and differentiated cells that are genetically and immunologically matched to the adult donor.

Until 2005, researchers had been frustrated in their attempts to duplicate with human cells the same success achieved with SCNT in many other mammalian species. Some researchers were considering the possibility that SCNT in humans would be for all practical purposes impossible. This view was apparently proven wrong when the laboratory of Dr. Hwang Woo Suk published a report demonstrating the successful derivation of stem cell lines from eleven separate cases of human SCNT (Hwang et al., 2005). Hwang, whose laboratory had cloned the first dog (Lee et al., 2005), was seen as so far ahead with SCNT that other laboratories around the world suspended attempts to achieve human SCNT, choosing instead to collaborate with Hwang’s laboratory. Unfortunately, the story began to unravel in late 2005 and by the next year, it was clear that the results announced in Dr. Hwang’s paper were entirely falsified (Kennedy, 2006). Because researchers throughout the world had chosen to not pursue SCNT, this line of research was set back a year or more. It wasn’t until 2008 that scientists at Stemagen successfully reported human SCNT (French et al., 2008)

Although SCNT has both scientific and therapeutic benefits, it still raises significant ethical questions, particularly because it depends on women who are willing and able to donate some of their eggs. Egg donation is not free of risk and, therefore, many bioethics committees and regulatory bodies have decided to err on the side of caution by prohibiting payment for eggs donated for the purposes of stem cell research. While on the one hand this position might be seen as paternalistic, the case can be made that any significant payment might lead those who are young or poor to overlook the possible risks of donation. The debate about payment is likely to continue, but it is clear that SCNT depends on a resource (human eggs) that is in limited supply and that can be obtained only through a time-consuming and invasive procedure.

An ongoing hope is that pluripotent cells might be found without the need for either human embryos or eggs. A number of reports have suggested that such cells might be found, for example, in amniotic fluid (De Coppi et al., 2007) and testes (Conrad et al., 2008). Another approach, reprogramming of adult cells, has been found to be far easier than expected and provisionally as good as or better than other sources of cells. In brief, cells (e.g., fibroblasts) are obtained from an individual, treated with a viral vector to introduce as few as 4 genes which, effectively, dedifferentiate (reprogram) the cells to become pluripotent stem cells (Takahishi et al., 2007; Yu et al., 2007). These cells are now commonly referred to as induced pluripotent stem (iPS) cells. Although these findings are intriguing, it remains to be seen whether the various alternative sources of pluripotent stem cells will prove to have the same qualities as the stem cells derived from human embryos (Hyun et al., 2007).

Regulations and Guidelines

In just ten years (1998-2008), the field of human embryonic stem cell research evolved rapidly. Almost certainly, because of intense public scrutiny, the landscape for regulations and guidelines has also evolved rapidly. Unfortunately, the regulatory environment for this research varies not only across international borders, but significant differences are found even among the states of the United States. It is neither useful nor possible to describe regulations in each of these jurisdictions both because of extensive variation and because regulatory changes continue to be driven by changing public opinion and rapid advances in the sciences. However, a few examples are useful to illustrate the complex and often conflicting approaches to stem cell research across international and interstate borders.

Internationally, the environment for stem cell research ranges from a virtual prohibition to a near absence of restriction (Isasi and Knoppers, 2006). Several countries, including Austria, Norway, and Poland, have prohibited any human embryo research. Others, such as the U.S. and Germany, prohibit the use of federal funds for hESC research, but in the face of public pressure both countries have adopted national policies that allow the use of federal funds for stem cell lines created before August 2001 and May 2007, respectively. Finally, for all practical purposes, China and Singapore are examples of countries with relatively few restrictions on hESC research.

The variation across international borders in stem cell regulations should not be taken as a sign that the international stem cell community has been silent about the responsible conduct of stem cell research. The International Society for Stem Cell Research (ISSCR), (one of the leading international stem cell research organizations, has established a variety of guidelines that are now widely accepted throughout the stem cell research community (ISSCR, 2006). Key principles of these guidelines are:

• "All experiments pertinent to human embryonic stem cell research that involve pre-implantation stages of human development, human embryos or embryonic cells, or that entail incorporating human totipotent or pluripotent cells into animal chimeras, shall be subject to review, approval and ongoing monitoring by a special oversight mechanism or body equipped to evaluate the unique aspects of the science. Investigators should seek approval through a process of Stem Cell Research Oversight (SCRO)."  
• "Given current scientific and medical safety concerns, attempts at human reproductive cloning should be prohibited."  
• "…privacy and confidentiality of personal information should be protected with the utmost care. Caution must also be taken to ensure that persons are not exploited during the procurement process, especially individuals who are vulnerable due to their dependent status or their compromised ability to offer fully voluntary consent. …there must be a reasonable relationship between those from whom such materials are received and the populations most likely to benefit from the research. Finally, the voluntary nature of the consent process must not be undermined by undue inducements or other undue influences to participate in research."

While the U.S. has significant restrictions on the use of federal funds for stem cell research, such research is still permitted to the extent allowed under state laws. As with international stem cell regulations, tremendous variation can be found among different states (National Conference of State Legislatures, 2008). As of 2008, South Dakota prohibits hESC research, while some states (e.g., California, New York) have been not only permissive of stem cell research, but have approved significant public funding dedicated to hESC research.

The fact that some states are highly permissive of stem cell research does not mean that such research occurs in the absence of either regulations or guidelines. Nationally, guidance that is generally accepted has come from the National Academy of Sciences. Following their initial report (Committee on Guidelines for Human Embryonic Stem Cell Research, 2005), the NAS has published amendments in 2007 and 2008 (Human Embryonic Stem Cell Research Advisory Committee, 2007 and 2008). Two key points in those guidelines are:

• "To provide oversight of all issues related to derivation and use of hES cell lines and to facilitate education of investigators involved in hES cell research, each institution should have activities involving hES cells overseen by an Embryonic Stem Cell Research Oversight (ESCRO) committee."
• "An IRB …should review all new procurements of all gametes, blastocyst, or somatic cells for the purpose of generating new…cell lines."

One of the states that have been most receptive to hESC research is California. In 2004, a significant majority of California voters approved Proposition 71, creating a mechanism for allocating $3 billion for stem cell research over a 10-year period. This voter-approved initiative also put in place a framework to promote scientific, legal, and ethical oversight for stem cell research through the creation of the California Institute for Regenerative Medicine (CIRM). The resulting requirements for CIRM-funded research have generally been extended to all stem cell research in California. Under California law (California Institute for Regenerative Medicine, 2008), key requirements for stem cell research include requirements for review of the research by the equivalent of an ESCRO Committee, criteria for the acceptable derivation of materials that are to be used for research use, and categories of research that are specifically prohibited.

Scientists and clinicians in a private institute (in another country) have reported the birth of a child who is a genetic clone of her mother. Using the same technology as was used to create Dolly the sheep, the scientists had taken the DNA from one of the future mother’s cells, and inserted that DNA into one of her eggs. The resulting cell was stimulated to begin dividing, resulting in a blastocyst (embryo) that could be implanted in the mother’s uterus. Nine months later, the first known human clone was born.  Karl is an assistant professor recently hired at Smalltown University. Karl’s primary research focus is human embryonic stem cells. He is using stem cell lines produced at other research institutions for his own studies to see if he can stimulate those cells to differentiate into nerve cells. Some of his experiments include transplanting those cells into mice to assess the factors that help those cells transform into human neurons integrated into the mouse brain. He is the only faculty member at SU working in stem cell research.  Roxie is a news reporter with the primary news outlet in Smalltown. She is typical of many of the residents of Smalltown, and believes that once an egg is fertilized it is the equivalent of a human life. Roxie has just received the report of the first human clone. Because she believes this story would be of significant interest to her readers, she contacts the press office at SU and asks to speak to a scientist about this report on human cloning. She is introduced to Karl, who is described as an expert in the field of stem cell research.  The questions Roxie brings to the interview are wide-ranging. Some of the initial questions are for background information: How does this technology work? How easy is it? She next asks questions about the cloned human, such as: Is it safe (what are the risks to the mother and child)? Is this legal in this country? Is it ethical to create human life in this way? Later, the interview turns to the work of Karl. Roxie is very concerned about experiments in which human nerve cells will be inserted into the brain of a mouse. She now asks about the possibility that the mouse will have a human brain: Will it be smarter? Will it be able to think like a human? Will it be a human trapped in the body of a mouse? And all of these questions then lead to some fundamental questions: Are scientists playing god when they conduct these kinds of experiments? Who decides which experiments will and won’t be done?  Assuming that Karl has agreed to do this interview, and you had a good idea what type of questions would be asked by Roxie, then how would you advise Karl about the things that he should and should not say and do in the interview?

• Describe three examples of potential benefits from human embryonic stem cell research that are less likely to be achieved by other available approaches.   
• Describe at least one instance in which misconduct or insensitivity to public concerns helped to increase opposition to human embryonic stem cell research. Identify federal or state regulations and guidelines that were apparently direct responses to such abuses.   
• What are the responsibilities of an ESCRO or SCRO Committee?   
• In your institution, what minimal changes (e.g., addition or removal of stem cell lines to be studied) to your protocol require review and approval of the ESCRO or SCRO Committee? What changes are of a magnitude to require submission, review, and approval of a new protocol?   
• If you observed another investigator abusing the privilege of stem cell research, who should be notified?   
• Describe your criteria for the acceptable use of human embryos and stem cells. Consider the importance and likelihood of benefits to be obtained, the source of the material being used (e.g., egg donation for SCNT vs. iPS cells), the nature of the proposed experiments (e.g., in vitro vs. insertion of human cells into a non-human species), and rationale for the proposed research (e.g., basic science, prevention or treatment of disease, or technology that would allow enhancement of an otherwise normal individual).  
• What forums are available in your institution to examine the ethical and/or legal ramifications of stem cell research? What, if anything, can you do to promote such discussion? 

Clearly, from an ethical perspective, stem cell research constitutes one of the most complex of the numerous domains of research. Many considerations might be listed here, but three seem to be particularly noteworthy.

• Public Scrutiny: Stem cell research is likely one of the most watched areas of academic endeavor in the history of academia. This is a direct consequence of two very different public perceptions of this research. Internationally, and certainly within the borders of the U.S., the majority of the public has recognized in this research a potential for a virtual revolution in medicine. It remains to be seen whether this will be the case, but this segment of the population is highly attentive and supportive of all that is happening in stem cell research. In addition, there is a second group, which is very much opposed to human embryonic stem cell research. While most polls and votes indicate that this group is in the minority, it is nonetheless a substantial minority. Among the members of this second group, there is a highly principled belief that harm or destruction of a human embryo is the equivalent of harm or destruction of a human child. For this group, the possible benefits of stem cell research cannot be on the table if those benefits in effect require the taking of human lives. For these reasons, this group is also watching stem cell research closely and seeking alternatives that do not require the use of human embryos. Scrutiny by both supporters and opponents of stem cell research places a higher obligation on stem cell researchers than for other areas of research. In short, mistakes by stem cell researchers are not likely to be overlooked. An ethical lapse, misuse of funds, or violation of regulations will not be merely a matter of individual concern. It is highly likely that such mistakes will reflect at least on the individual’s institution, and also on all of stem cell research, if not science in general.
• Special Respect: A case can be made that the human embryo deserves special respect (Robertson, 1999). At first glance, such a statement may seem unnecessary to supporters of stem cell research and hypocritical to its opponents. Stem cell researchers might argue that since the majority of the public favors such research, and presuming that the researchers are working in a jurisdiction that makes such research legal, then they should no longer have to give any more consideration to human embryos or eggs than they might give any other human cell. Conversely, opponents who view the human embryo as a human life might argue that "special respect" is meaningless if the embryo is still going to be harmed or destroyed. There is, however, a middle ground between these views. As implied by Robertson’s argument (1999), respect does not have to be absolute; it can be in varying degrees. Such respect may not mean that we will abandon human embryonic stem cell research, but we still can and should recognize that it is a privilege to conduct this research. The circumstances under which human eggs or embryos are made available to research are anything but trivial. Under those circumstances, we recognize the precious nature of those human cells. That privilege is one that cannot be taken lightly. In fact, most of us already have internalized a recognition of the differential value we would place on a developing embryo, a fertilized egg, an egg, or sperm. For example, if only some, but not all, of the above could be saved in the face of imminent danger, most of us are likely to put the greatest value on the embryo. In practice, this special value means that we have an obligation to ensure that those cells are put to the best possible use in a project that has been reviewed and approved for ethical, legal, and scientific merit.  
• Origins and Uses: Because much of the debate about human embryonic stem cell research has focused on the embryo, it is easy to overlook that this is not the only ethical challenge requiring consideration. While the origins of stem cells are important and cannot be dismissed, we must also ask about the ethical challenges in the conduct of basic and clinical stem cell research. Many such considerations are characteristic of any research (e.g., standards for recordkeeping, sharing of data, addressing conflicts of interest, or allocating credit), but some issues are specific to stem cell research. Two areas that are of particular note are chimeras and clinical trials. Chimeras:  A chimera is defined in various ways, but the principle is that one organism consists of components that are demonstrably derived from two or more distinct species. The name chimera comes from a monster in Greek mythology that was a combination of different animals (typically a lion, goat, and snake). In biology, chimeras can now be formed either by inserting cells from one species into the adult of another species, or by creating an embryo that begins with cells from two or more species. In principle, it seems that our society already accepts the possibility of saving a child’s life by replacing a defective heart with one that is non-human (e.g., a baboon heart, Altman, 1984), but we are much less comfortable with creating a non-human animal that might have human features (e.g., a human face, ear, or hand). Having the appearance of a human is problematic more because of our discomfort than because it necessarily raises some direct ethical dilemma. However, we have reason to be much more concerned about a human nervous system (i.e., do we have a risk of a non-human animal achieving levels of awareness and understanding that would make it sufficiently human to be deserving of human protections?) or human gametes (i.e., do we have a risk of two non-human animals reproducing with human gametes, thereby producing a human, or largely human, organism?). These questions are very much hypothetical and, if not impossible, highly improbable under the circumstance that the ethical, legal, scientific, and social environment is not one that favors these goals. Nonetheless, responsible science and policy require that one concern for reviewers of stem cell research is to address the potential risks with experiments that involve the mixing of stem cells from two or more species. Clinical Trials:  In the very near future, we are likely to see clinical trials based on reputable, pluripotent stem cell research. We are already seeing numerous stem cell "trials" worldwide that are arguably questionable, and sometimes criminal. By taking advantage of public awareness of and excitement about stem cell research, it is now possible to find groups that will offer to treat or cure almost anything in the context of a clinical "trial" that typically has no control group and for which participants must pay for participation. Payments for such "trials" are often on the order of $10,000 or more. Whether intentional or not, these trials are likely to be scams with little chance of success. Particularly under these circumstances, the stem cell field must meet a higher than average standard before approving the first clinical trials with this very new approach to treating disease. To do otherwise risks a backlash against all of stem cell research if initial trials unexpectedly result in a worsening of disease, serious side effects, or even death. All of these are possible outcomes no matter how much work has been done before the first trials in humans. Therefore to decrease that risk the scientific community can and should set a high bar both for the circumstances under which such a trial should be attempted and for the design of the research study to ensure the highest level of protections for informed consent and the welfare of the research participants.
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• Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V, Jones J (1998): Embryonic stem cell lines derived from human blastocysts." Science 282 (5391): 1145-7.
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Advances in Induced Pluripotent Stem Cell Research

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• v.16(7); 2021 Jul 13

Recognizing the ethical implications of stem cell research: A call for broadening the scope

Lars s. assen.

1 Julius Center for Health Sciences and Primary Care, Department of Medical Humanities, University Medical Center Utrecht, 3508 GA Utrecht, the Netherlands

Karin R. Jongsma

Rosario isasi.

2 Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 3310, USA

Marianna A. Tryfonidou

3 Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 CM Utrecht, the Netherlands

Annelien L. Bredenoord

The ethical implications of stem cell research are often described in terms of risks, side effects, safety, and therapeutic value, which are examples of so-called hard impacts. Hard impacts are typically measurable and quantifiable. To understand the broader spectrum of ethical implications of stem cell research on science and society, it is equally important to recognize soft impacts. Soft impacts are the effects on behavior, experiences, actions, moral values, and social structures; these are often indirect effects of stem cell research. The combined notions of hard and soft impacts offer a broader way of thinking about the social and ethical implications of stem cell research and can help to steer stem cell research into a sociable desirable direction. Soft impacts enable researchers to become more aware of the broad range of significant implications involved in their work and deserve equal attention for understanding such ethical and societal effects of stem cell research.

The ethical implications of stem cell research are often discussed in terms of risks, side effects, and safety, which are examples of hard impacts. In this article, Assen and colleagues argue that to understand the broader spectrum of ethical implications of stem cell research on science and society, it is important to recognize the so-called soft impacts.

Introduction

Stem cell science has expanded in the past two decades. These new research possibilities raise ethical and policy questions. While ethical reflections on embryonic stem cells have strongly focused on the moral status of the embryo, this is not the case with induced pluripotent stem cells (iPSCs) and adult stem cells. Ethical reflections surrounding these types of stem cells focus primarily on risks of stem cell interventions, what kind of harm unproven stem cell interventions could cause, how to seek informed consent of patients, and questions about ownership ( Andrews et al., 2015 ; Hyun, 2010 ; King and Perrin, 2014 ; MacPherson and Kimmelman, 2019 ). However, stem cell research has other important ethical implications that are easily overlooked.

For example, between 2013 and 2014, clinical researchers conducted a first-in-human study with a mix of allogeneic mesenchymal stem cells and autologous chondrons as an intervention for stimulating autologous cartilage repair in the knee, with promising results ( de Windt et al., 2017 ). During the clinical trial, there were drawbacks in the recovery of some participants. They did not adhere to the instructions of the researchers to be careful with burdening their knee too much, which inadvertently negatively influenced their rehabilitation process. Possibly, some of the patients believed that the stem cell intervention was more effective than it really was. The drawback was not a direct effect of the stem cell intervention itself. It was an effect of how the stem cell intervention affected patient’s beliefs about the therapeutic value that resulted in an undesirable and unforeseen effect of this intervention. Such a mistaken belief in which the research participant overestimates the benefits of the intervention is often referred to as therapeutic misestimation ( Habets et al., 2016 ; Horng and Grady, 2003 ). This belief can have several causes; it could, for example, have been a result of the positive portrayal of stem cell research in the media ( Caulfield et al., 2016 ). The researchers of the aforementioned study adhered to ethical guidelines, including approval by the Dutch Central Committee on Research Involving Human Subjects, proper informed consent procedures, and taking preventive measures to minimize or mitigate possible harm ( de Windt et al., 2017 ). Despite good preparations and preventive measures, the drawback in recovery was undesirable and, in hindsight, to some extent avoidable. In subsequent studies, researchers and physical therapists used the described example to stress to patients the importance of being careful with mobilizing their knee after surgery.

This example indicates that the existing narrow view of ethical considerations fails to do justice to all ethical implications related to the use and integration of stem cells in society. This view focuses primarily upon issues, such as the harm of unproven stem cell interventions, and side effects, such as teratoma formation, storage of donated tissue, and discussions about ownership ( Andrews et al., 2015 ; Hyun, 2010 ; King and Perrin, 2014 ; MacPherson and Kimmelman, 2019 ). Stem cell research could benefit from a broader conception of ethical considerations, which could contribute to developing effective strategies to enhance the benefits of stem cells and mitigate undesirable effects. This broader conception of ethical implications can be promoted by distinguishing between the narrow view as “hard impacts,” and a type of ethical considerations that is now often being overlooked, referred to as “soft impacts” ( Swierstra, 2015 ; Swierstra and te Molder, 2012 ; van der Burg, 2009 ). The terms hard and soft do not refer to the severity of the impact, but to what is actually impacted.

Hard impacts are characterized by two aspects ( Swierstra, 2015 ). First, there is a causal physical relationship between the research, intervention, or technology, and the effect it has. For example, how a drug (technology) improves the health (the effect), or how a drug leads to an undesirable side effect. Second, the research or technology outcome is quantifiable and measurable, such as the gravity of an immune response, the type of gene-expression pattern of stem cell lines ( Scudellari, 2016 ), and the costs to clinically translate stem cell research ( Neofytou et al., 2015 ). These outcomes could, for instance, indicate an increase or decrease in harm. In other words, hard impacts are direct (physical) outcomes or financial effects of the research, technology, or intervention. It often includes risks, side effects, costs, safety, and therapeutic value. These impacts can be both positive and negative for individuals and society.

Soft impacts are characterized by how technologies, research, or interventions affect experiences, perceptions, actions, social structures, and/or moral values, and are therefore not easily quantifiable or measurable ( van der Burg, 2009 ). In that respect soft impacts are often about the psychological and social effects of research and technology. Compared with hard impacts, soft impacts are outcomes that are an indirect effect of research or technology. An overview of potential hard and soft impacts can be found in Table 1 .

Potential hard and soft impacts of stem cell research and stem cell-based interventions

This paper argues that the notion of soft impacts could help stem cell researchers to become more aware of the wider array of ethical implications involved in their work. The combined notions of hard and soft impacts offer a broader way of thinking about the ethical implications of stem cell research and can help to steer stem cell research and innovation into a desirable direction. Therefore, these terms will be used in this paper as a heuristic tool to exemplify the different ways of thinking about ethical implications of stem cell research and interventions. Taking both types of impacts into account could have merits for responsible development, use, and policy of stem cell interventions.

Hard and soft impacts: Examples

To illustrate the difference of hard and soft impacts of stem cell research, we draw on organoid research as an example and its impacts on personalized medicine, costs, and animal research. An organoid is defined as an in-vitro -generated stem cell-derived structure, mimicking the architecture and physiology of intact organs. These organoids can, among others, be derived from iPSCs and adult stem cells and it has been proven to be a suitable model for disease-modeling research ( Bredenoord et al., 2017 ; de Souza, 2018 ).

A positive hard impact of this type of technology is that it allows for the creation of new types of personalized interventions, with an increased therapeutic value compared with non-personalized interventions, thereby reducing harm. In terms of quality adjusted life years (QALYs), personalized interventions could be cost-effective ( Hatz et al., 2014 ). However, since personalized medicine may lead to an increase in QALYs compared with conventional alternatives, it is likely that overall costs will also increase ( Tiriveedhi, 2018 ). Therefore, the development of organoids for personalized interventions may also increase the overall costs for healthcare. This financial harm is a possible negative hard impact of the success side of this technology.

By focusing merely on the increasing costs of medical research and innovations, one may overlook the soft impacts and how technological developments are embedded in a broader social context. Within this context, organoid research used in personalized medicine could potentially affect the financial sustainability of solidarity-based healthcare systems. An example of solidarity in healthcare is the collective responsibility for paying the costs in healthcare ( Ter Meulen and Maarse, 2008 ). Here, the insured population contributes with a relatively small amount of money that is reserved for paying the total or a (large) part of society's healthcare costs. When organoid research-based innovations indeed lead to considerably increased healthcare costs, it could affect the surrounding system of solidarity and consequentially our attitudes to others.

The differences between hard and soft impacts are as well highlighted in the example of how organoid technology affects animal research. A possible hard impact of organoid research is reduction and/or replacement of animal studies, two of the 3Rs principles (refinement, reduction, and replacement) that contribute to ethical research ( Bredenoord et al., 2017 ). Animal studies have been considered necessary and acceptable—even if controversial—for conducting safety and efficacy studies. Within this context, a conceivable soft impact of organoid technology is that it could affect how animal studies are perceived . Taking the 3Rs of animal studies in mind as an ethical ground rule, it is possible that the ethical acceptability of certain animal studies will be assessed differently because of the possibility to test efficacy and safety by means of organoids. Two concepts are relevant here: subsidiarity and proportionality ( Jans et al., 2018 ). Subsidiarity implies that an action is acceptable because that action is the least morally problematic way of performing research. In that light, organoid technology is generally considered less morally problematic than research on experimental animals. Also, the proportionality of animal research is relevant to consider. This refers to the question whether animal research for testing the effectiveness and safety of new therapies is still proportional ( Jans et al., 2018 ). In the past, studies in which harm was inflicted on animals were considered proportional for acquiring insights into the safety and efficacy of interventions. Nowadays, with organoid technology, animal testing could in certain cases be perceived as disproportional, since it may not be necessary to inflict harm on animals for acquiring insights in efficacy and safety. Therefore, the existence of organoid technology can affect the permissibility of using certain animal studies. Important to note is that, while the field is evolving toward animal-free substitutes, organoid studies are often also not completely “animal-free.” This is due to the fact that Matrigel, which is commonly used to provide the cells with a 3D environment in which they can thrive, is derived from mice ( Bredenoord et al., 2017 ).

By considering hard impacts of a technology or intervention we find multiple advantages. Quantifying outcomes and the assessment of directs risks help to develop safety measures to prevent harm to the health and well-being of patients and research participants. Furthermore, it helps to create a picture of the financial costs. However, quantifying diseases, cells, side effects, and costs, is only part of the ethical implications of these interventions, as the above-mentioned examples explicate. A narrow focus on hard impacts alone comes with the risk of ignoring aspects that are important for the success and acceptance of these interventions. The effect of technology co-producing our morality, such as solidarity and the perception of animal research, is often referred to as “techno-moral change” ( Swierstra, 2015 ). Insights into this techno-moral change through considering soft impacts could contribute to dealing with the ethical challenges of stem cell research. Being oblivious to the soft impacts of technologies and interventions means that the personal and societal effects are missed.

Implications for stem cell research(ers)

Becoming aware of the soft impacts of stem cell research could help researchers to anticipate ethical implications and to develop new skills. As a result, researchers could benefit from soft impacts to positively impact the quality of research; it provides a way of anticipating and understanding the ethical implications of stem cell technologies.

Funding agencies focus increasingly on the social value of research, thereby making it more relevant for researchers to contemplate social value and impact. Soft impacts can help to analyze the social value of research. Focusing on soft impacts enables to not only look at treatment effects on a disease or saving money, but also how the research could potentially improve societal structures and increase social justice. For example, the social value of stem cell research could be that it promotes social justice or helps to empower a group of patients (e.g., destigmatize or physically benefit and enable more participation in society) and helps the target group to flourish.

To better anticipate the ethical dimensions of stem cell research and stem cell-based interventions, we need scientists who recognize both hard and soft impacts. To this end, training or educating in terms of hard and soft impacts could be a tool for recognizing the ethical implications of stem cell research and a step toward contemplating whether to mitigate, prevent, or stimulate certain soft impacts. This could, for instance, be done by creating or implementing courses in biomedical curricula that involve how early patient involvement could be achieved, how the public could be engaged, and what the ethics of biomedical research involve. To prevent that these courses reinforce the focus on hard impacts, ethical training or education should be broadened by reflecting upon how stem cell research affects experiences, perceptions, actions, social structures, and moral values.

Patients can offer valuable insights into how stem cell research could affect perceptions, expectations, and actions. Engaging with patients could give insights into how their disease creates specific drawbacks and expectations. Doing this in an early stage of the research, could aid researchers in preventing the negative and foster the positive impacts in a timely manner ( Supple et al., 2015 ). Courses should address under which conditions early patient involvement is fruitful, how and when this could be implemented in the study design, and which skills are needed to have meaningful interactions with patients.

Similarly, public engagement and science communication could be addressed in curricula or workshops. Ideally, this should lead to interactions and dialogue where there is room for the concerns of the public ( Reincke et al., 2020 ). Such interactions could provide information about possible social and societal implications of stem cell research. Courses should focus upon how such dialogue could be organized and on skills that foster dialogue and lay translation of research.

Furthermore, education about the ethics of biomedical research can stimulate moral awareness by researchers. Using not only factual information but also vignettes and moral scenarios ( Swierstra, 2015 ) can offer insights in how stem cell research could affect social practices, moral values, or social structures. Other possible enabling methods are organizing interventions within research teams and using games and roleplay. These could be embedded in PhD programs and conference workshops. Altogether, these types of activities may promote the moral imagination ( Coeckelbergh, 2006 ) of researchers and students and thereby help them to learn to think about the soft impacts of their work. By doing so, moral imagination could help to understand and anticipate techno-moral change: the way that technology and morality co-shape each other ( Swierstra, 2015 ). It should be noted that educational research about the desired content and design is necessary.

Moreover, the notion of hard and soft impacts establishes a vocabulary and a broader way of looking at and reflecting on implications of stem cell technology. These insights could serve as a starting point for discussions about responsible and desirable stem cell science and what would be needed to create these circumstances.

Implications for policy and regulation

Regulation clusters a broad range of rules or principles governing and evaluating human behavior, thereby establishing boundaries between what should be considered acceptable or indefensible actions. As regulation is influenced by local historical, socio-cultural, political, and economic factors, assessing the hard and soft impacts in both policy debates and outcomes contributes to the development of robust regulation. By doing so, regulation not only reflects society’s shared moral values, but also truly takes into account the broad range of impacts for individuals, communities, and societies. Thus, focusing solely on hard impacts is too narrow, as other important factors for the responsible development and use of stem cell interventions can be overlooked.

To advance responsible development of stem cell interventions, an important question is whether new rules and legislation for promoting ethically sound research should be implemented or how much leeway organizations and researchers should have to deal with the impacts themselves. Rules and regulation might be helpful for conceptualizing and adherence to responsibilities ( Coeckelbergh, 2006 ). For instance, the ISSCR (International Society for Stem Cell Research) provides guidelines for safety and efficacy studies, and guidelines for the derivation, banking, and distribution of stem cell lines. This already helps to prevent and mitigate certain hard impacts of stem cell research, such as loss of reliable data due to contamination of stem cell lines and privacy issues in biobanking ( International Society for Stem Cell Research (ISSCR), 2016 ). As such, guidelines, rules, and regulations help to allocate accountability for processes or operations to researchers or groups of researchers and establish international standards. However, this approach has its limitations, since guidelines, rules, and regulations tend to focus on moral impacts that are measurable or quantifiable. When soft impacts are framed in guidelines, rules, and regulations, we risk that possible socio-ethical challenges might be overlooked. Therefore, guidelines, rules, and regulations cannot and should not do all the moral work. It is important to articulate and explicate the ethical dimensions in stem cell research, where it could help researchers to make better decisions about how the research could be conducted in a desirable and responsible manner. The latter in turn, could ultimately be translated in improved policies or regulations.

Concluding remarks

So far, academic literature, policy, and researchers have focused primarily on hard impacts of stem cell research. Ethical reflection on stem cell research and technology could be broadened by focusing on soft impacts as well. While the term “soft” may sound misleading as being insignificant, the soft impacts are influential for the use and acceptance of these technologies and require more academic and regulatory attention. Broadening the scope of ethical reflection has implications for education, policy, and regulation. The challenge is to find a balance between how much freedom and education researchers should have to deal with possible ethical implications themselves and where policy and regulation could be of help.

It should be noted that, while hard and soft impacts are meaningful heuristic tools to broaden the scope of ethical implications one could assess, the distinction between hard and soft impacts is primarily an analytical distinction, and not always crystal clear ( Swierstra, 2015 ). For instance, certain soft impacts could become hard impacts over time. Nonetheless, anticipating both hard and soft impacts could steer research and innovation into a desirable direction.

More importantly, having a more comprehensive understanding of the ethical implications of stem cell research could help researchers and others to think about how to anticipate and thereby possibly prevent or mitigate possible future challenges instead of dealing with ethical challenges once they emerge.

Acknowledgments

This project has received funding from the European Union's Horizon 2020 research and innovation program iPSpine under grant agreement no. 825925. M.A.T. receives funding from the Dutch Arthritis Society (LLP22). We thank Roel Custers and Lucienne Vonk for sharing their experiences with us and we would like to thank our colleagues at the UMCU for commenting on early draft versions of the paper. Moreover, we thank the anonymous reviewers for their constructive feedback.

Author contributions

L.S.A., K.R.J., and A.L.B. conducted the initial desk research and prepared the first draft of the manuscript. M.A.T. and R.I. commented on and contributed to several draft versions. L.S.A. prepared the final manuscript for submission. All authors approve of the final version.

Conflicts of interests

M.A.T. is a member of the scientific advisory board of JOR Spine board and a scientific advisor for CentryX.

A.L.B. is a member of IQVIA's Ethics Advisory Panel. A.L.B. and R.I. are members of the Ethics Committee of ISSCR.

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Unlocking the ‘chain of worms’

Scientists share single-cell atlas for the highly regenerative worm, Pristina leidyi

An international team of scientists including B. Duygu Özpolat at Washington University in St. Louis has published the first single-cell atlas for Pristina leidyi (Pristina), the water nymph worm, a segmented annelid with extraordinary regenerative abilities that has fascinated biologists for more than a century.

Annelid worms — including the most familiar among them, the earthworms — are a broadly distributed, highly diverse, economically and environmentally important group of animals.

Most annelids can regenerate missing body parts, and many are able to reproduce asexually. But the adult stem cell populations involved in these processes, as well as the diversity of cell types generated by the stem cells, have remained unknown.

This particular worm, Pristina, first caught the eye of biologists in the 1800s and has remained an object of much interest. Under laboratory conditions, Pristina grows very rapidly and creates copies of itself by asexual reproduction.

Using a mechanism called paratomic fission, the worm starts forming and differentiating new head and tail segments from within a single body segment, producing what is known as a “chain of worms.” Eventually these clones separate and become distinct individuals.

“These worms are constantly generating all body parts and therefore all adult cell types,” said Özpolat, an assistant professor of biology in Arts & Sciences.

In all, the new single-cell atlas for this worm assembles 75,218 single-cell transcriptomes characterizing all major annelid cell types, including complex patterns of regionally expressed genes in the annelid gut, as well as neuronal, muscle and epidermal specific genes. The study is published in Nature Communications .

“We want to understand how different organisms like Pristina have evolved to continuously grow throughout their lives and regenerate, the nature of cells involved in these processes, and molecular signatures they have,” Özpolat said.

“Different organisms have evolved different strategies,” she said. “The cellular and genetic mechanisms we learn from the worms not only help us understand these fascinating organisms better, but can also inform stem cell technologies and regenerative medicine down the line.”

“It is curious that these worms can maintain adult stem cells indefinitely,” Özpolat said.

“We have grown thousands of clones from a single individual, and our worm cultures are still going strong.”

Segmented reality

Özpolat produced and mapped the single-cell atlas for Pristina in partnership with Jordi Solana at University of Exeter in the United Kingdom and Patricia Álvarez-Campos at Universidad Autónoma de Madrid. Solana and his group had previously focused on stem cells in a different type of worm: the planarian, or flatworm.

Pristina was a new challenge for the combined team to take on. Annelids like Pristina have bodies that are made up of a series of segments with a growth zone at the tail end which produces new segments continuously from two concentric rings of stem cells.

And then there was Pristina’s unusual tendency to bud, or make a chain.

“When the animal reaches a certain size, then it somehow senses that it has reached the threshold to split,” Özpolat said. “And so, it starts making a head and then a new tail in the middle of its body. This means it has to completely reorganize what used to be a segment that contained the intestine into a segment that now will have a new brain, or new ovaries and testes.”

As a postdoctoral scholar, Özpolat was most interested in how worms made new gonads as part of this chain-like reproductive process.

For her future research directions, she plans to also focus on the gut.

“With single-cell atlases, you take an entire organism and you literally split it into its individual cells. And then you look at gene expression in each cell separately,” she said. “Then you group them into these maps, based on their similarities in terms of gene expression patterns.

“We found cell types that we didn’t even know that existed in this animal,” Özpolat said. “Its gut is so neatly organized and specific. There are about 12 different gut cell types in this tiny little worm, which will be very interesting for future projects we’re already working on.

“It just opens up so many doors now that you can visualize these different cell types, and how they behave during fission and regeneration,” she said.

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Stem Cell Research

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In recent years, biomedical research has been significantly altered by technologies for the derivation of human cell lines capable of differentiation into any of the cells of the human body. Such cells are sometimes called "pluripotent" because they have the power ("potency") to become many ("pluri-") different cells. It has long been known that such cells exist, but it wasn�t until 1981 that stem cells were isolated from mouse embryos (Evans and Kaufman, 1981; Martin, 1981), and only in 1998 that the derivation of human embryonic stem cells was first reported (Thomson et al., 1998). This tool was quickly recognized as an opportunity to better understand normal and pathological human development, to identify and test new pharmacological therapies, and perhaps to even replace diseased tissues or organs. Many scientists viewed this as a potentially revolutionary approach to studying human biology. However, because a necessary first step was to use and destroy human embryos such research raised serious questions for some members of the public, as well as some scientists.

Opposition to Stem Cell Research

While most hESC scientists view the human embryo as human cells with great biological and scientific potential, there are many members of our society who hold religious beliefs that define the human embryo as equivalent to a human life. By this view, any harm or destruction of the human embryo is tantamount to harm or destruction of a human life. This perspective has become more than a matter of personal opinion. For many years now, under the Dickey amendment (1995), the U.S. Congress has agreed to federal restrictions on any research that would require harm or destruction of the human embryo. This restriction was partially lifted in 2001 by President Bush�s announcement that research with stem cell lines existing as of August 9, 2001 could be eligible for federal funding.

Subsequently, President Obama annouced a new approach to approving stem cell lines for federal funding (Obama, 2009). The question now is not whether stem cell lines were created before a particular date, but whether or not those lines meet criteria that have been defined for ethically derived stem cell lines (NIH, 2009). While the result has been an increase in the number of stem cell lines approved for federal funding, it is noteworthy that the number of lines meeting these criteria is limited (NIH Human Embryonic Stem Cell Registry). In fact, many of the lines approved under the Bush policy are not acceptable under the Obama guidelines.

It would be a mistake to assume that religion is the only basis for arguments against hESC research. It is clear that some individuals and groups are motivated more by philosophical, political, or even economic arguments. However, whether based on religion or otherwise, most polls show that opponents to hESC research may represent a minority, but that minority is substantial in size and in impact (e.g., pollingreport.com).

Sources of Stem Cells

Stem cells can be obtained from embryos, but embryos are only one of many potential sources. In the fetus, and even in an adult, stem cells can be found in many body tissues. The best known of these sources is bone marrow, in which stem cells are produced that are capable of differentiating into different types of blood ells. However, these stem cells are not pluripotent as defined above. Such cells are often called adult or tissue-specific stem cells. These cells have important, but restricted, clinical applications distinct from the wider range of possibilities with human embryonic stem cells (Wood, 2005).

Several sources of pluripotent stem cells have now been identified. One of these sources is based on the technology used to clone �Dolly� the sheep (Campbell et al., 1996), �Snuppy� the dog (Lee et al., 2005), and many other mammalian species. The first step to cloning these animals is a technique called Somatic Cell Nuclear Transfer (SCNT). SCNT in any species begins with an egg of that species from which the genetic material is removed. This egg can then be fused with an adult cell of the individual to be cloned. The result is an egg that now contains a full complement of DNA. Under appropriate laboratory conditions, that egg can be induced to divide as if it were a fertilized egg. If allowed to progress far enough, the resulting embryo can be implanted in the uterus of an individual of the same species, potentially resulting in the birth of a clone. However, it is also possible to allow the �embryo� to develop only for the purpose of harvesting stem cells rather than implantation. This source of stem cells is particularly important for stem cell research as well as potential therapies because of the opportunity to produce stem cells and differentiated cells that are genetically and immunologically matched to the adult donor.

Until 2005, researchers had been frustrated in their attempts to duplicate with human cells the same success achieved with SCNT in many other mammalian species. Some researchers were considering the possibility that SCNT in humans would be for all practical purposes impossible. This view was apparently proven wrong when the laboratory of Dr. Hwang Woo Suk published a report demonstrating successful derivation of stem cell lines from eleven separate cases of human SCNT (Hwang et al., 2005). Hwang, whose laboratory had cloned the first dog (Lee et al., 2005), was seen as so far ahead with SCNT that other laboratories around the world suspended attempts to achieve human SCNT, choosing instead to collaborate with Hwang�s laboratory. Unfortunately, the story began to unravel in late 2005 and by the next year it was clear that the results announced in Dr. Hwang�s paper were entirely falsified (Kennedy, 2006). Because researchers throughout the world had chosen to not pursue SCNT, this line of research was set back a year or more. It wasn�t until 2008 that scientists at Stemagen successfully reported human SCNT (French et al., 2008)

Although SCNT has both scientific and therapeutic benefits, it still raises significant ethical questions, particularly because it depends on women who are willing and able to donate some of their eggs. Egg donation is not free of risk and, therefore, many bioethics committees and regulatory bodies have decided to err on the side of caution by prohibiting payment for eggs donated for the purposes of stem cell research. While on the one hand this position might be seen as paternalistic, the case can be made that any significant payment might lead those who are young or poor to overlook the possible risks of donation. The debate about payment is likely to continue, but it is clear that SCNT depends on a resource (human eggs) that is in limited supply and that can be obtained only through a time-consuming and invasive procedure.

An ongoing hope is that pluripotent cells might be found without the need for either human embryos or eggs. A number of reports have suggested that such cells might be found, for example, in amniotic fluid (De Coppi et al., 2007) and testes (Conrad et al., 2008). Another approach, reprogramming of adult cells, has been found to be far easier than expected and provisionally as good as or better than other sources of cells. In brief, cells (e.g., fibroblasts) are obtained from an individual, treated with a viral vector to introduce as few as 4 genes which, effectively, dedifferentiate (reprogram) the cells to become pluripotent stem cells (Takahishi et al., 2007; Yu et al., 2007). These cells are now commonly referred to as induced pluripotent stem (iPS) cells. Although these findings are intriguing, it remains to be seen whether the various alternative sources of pluripotent stem cells will prove to have the same qualities as the stem cells derived from human embryos (Hyun et al., 2007).

In just ten years (1998-2008), the field of human embryonic stem cell research evolved rapidly. Almost certainly, because of intense public scrutiny, the landscape for regulations and guidelines has also evolved rapidly. Unfortunately, the regulatory environment for this research varies not only across international borders, but significant differences are found even among the states of the United States. It is neither useful nor possible to describe regulations in each of these jurisdictions both because of extensive variation and because regulatory changes continue to be driven by changing public opinion and rapid advances in the sciences. However, a few examples are useful to illustrate the complex and often conflicting approaches to stem cell research across international and interstate borders.

Internationally, the environment for stem cell research ranges from a virtual prohibition to a near absence of restriction (Isasi and Knoppers, 2006). Several countries, including Austria, Norway, and Poland, have prohibited any human embryo research. Others, such as the U.S. and Germany, prohibit the use of federal funds for hESC research, but in the face of public pressure both countries have adopted national policies that allow the use of federal funds for stem cell lines created before August 2001 and May 2007, respectively. Finally, for all practical purposes, China and Singapore are examples of countries with relatively few restrictions on hESC research.

While the U.S. has significant restrictions on the use of federal funds for stem cell research, such research is still permitted to the extent allowed under state laws. As with international stem cell regulations, tremendous variation can be found among different states (National Conference of State Legislatures, 2008). As of 2008, South Dakota prohibits hESC research, while some states (e.g., California, New York) have been not only permissive of stem cell research, but have approved significant public funding dedicated to hESC research.

One of the states that has been most receptive to hESC research is California. In 2004, a significant majority of California voters approved Proposition 71, creating a mechanism for allocating $3 billion for stem cell research over a 10-year period. This voter approved initiative also put in place a framework to promote scientific, legal and ethical oversight for stem cell research through the creation of the California Institute for Regenerative Medicine (CIRM). The resulting requirements for CIRM-funded research have generally been extended to all stem cell research in California. Under California law (California Institute for Regenerative Medicine, 2008), key requirements for stem cell research include requirements for review of the research by the equivalent of an ESCRO Committee, criteria for acceptable derivation of materials that are to be used for research use, and categories of research that are specifically prohibited.

Case Studies

Discussion questions, additional considerations.

Clearly, from an ethical perspective, stem cell research constitutes one of the most complex of the numerous domains of research. Many considerations might be listed here, but three seem to be particularly noteworthy.

• Public Scrutiny: Stem cell research is likely one of the most watched areas of academic endeavor in the history of academia. This is a direct consequence of two very different public perceptions of this research. Internationally, and certainly within the borders of the U.S., the majority of the public has recognized in this research a potential for a virtual revolution in medicine. It remains to be seen whether this will be the case, but this segment of the population is highly attentive and supportive of all that is happening in stem cell research. In addition, there is a second group, which is very much opposed to human embryonic stem cell research. While most polls and votes indicate that this group is in the minority, it is nonetheless a substantial minority. Among the members of this second group, there is a highly principled belief that harm or destruction of a human embryo is the equivalent of harm or destruction of a human child. For this group, the possible benefits of stem cell research cannot be on the table if those benefits in effect require the taking of human lives. For these reasons, this group is also watching stem cell research closely and seeking alternatives that do not require the use of human embryos. Scrutiny by both supporters and opponents of stem cell research places a higher obligation on stem cell researchers than for other areas of research. In short, mistakes by stem cell researchers are not likely to be overlooked. An ethical lapse, misuse of funds, or violation of regulations will not be merely a matter of individual concern. It is highly likely that such mistakes will reflect at least on the individual�s institution, and also on all of stem cell research, if not science in general.
• Special Respect: A case can be made that the human embryo deserves special respect (Robertson, 1999). At first glance, such a statement may seem unnecessary to supporters of stem cell research and hypocritical to its opponents. Stem cell researchers might argue that since the majority of the public favors such research, and presuming that the researchers are working in a jurisdiction that makes such research legal, then they should no longer have to give any more consideration to human embryos or eggs than they might give any other human cell. Conversely, opponents who view the human embryo as a human life might argue that "special respect" is meaningless if the embryo is still going to be harmed or destroyed. There is, however, a middle ground between these views. As implied by Robertson�s argument (1999), respect does not have to be absolute; it can be in varying degrees. Such respect may not mean that we will abandon human embryonic stem cell research, but we still can and should recognize that it is a privilege to conduct this research. The circumstances under which human eggs or embryos are made available to research are anything but trivial. Under those circumstances, we recognize the precious nature of those human cells. That privilege is one that cannot be taken lightly. In fact, most of us already have internalized a recognition of the differential value we would place on a developing embryo, a fertilized egg, an egg, or sperm. For example, if only some, but not all, of the above could be saved in the face of imminent danger, most of us are likely to put greatest value on the embryo. In practice, this special value means that we have an obligation to ensure that those cells are put to the best possible use in a project that has been reviewed and approved for ethical, legal, and scientific merit.
• Origins and Uses: Because much of the debate about human embryonic stem cell research has focused on the embryo, it is easy to overlook that this is not the only ethical challenge requiring consideration. While the origins of stem cells are important and cannot be dismissed, we must also ask about the ethical challenges in the conduct of basic and clinical stem cell research. Many such considerations are characteristic of any research (e.g., standards for recordkeeping, sharing of data, addressing conflicts of interest, or allocating credit), but some issues are specific to stem cell research. Two areas that are of particular note are chimeras and clinical trials. Chimeras: A chimera is defined in various ways, but the principle is that one organism consists of components that are demonstrably derived from two or more distinct species. The name chimera comes from a monster in Greek mythology that was a combination of different animals (typically a lion, goat, and snake). In biology, chimeras can now be formed either by inserting cells from one species into the adult of another species, or by creating an embryo that begins with cells from two or more species. In principle, it seems that our society already accepts the possibility of saving a child�s life by replacing a defective heart with one that is non-human (e.g., a baboon heart, Altman, 1984), but we are much less comfortable with creating a non-human animal that might have human features (e.g., a human face, ear, or hand). Having the appearance of a human is problematic more because of our discomfort than because it necessarily raises some direct ethical dilemma. However, we have reason to be much more concerned about a human nervous system (i.e., do we have a risk of a non-human animal achieving levels of awareness and understanding that would make it sufficiently human to be deserving of human protections?) or human gametes (i.e., do we have a risk of two non-human animals reproducing with human gametes, thereby producing a human, or largely human, organism?). These questions are very much hypothetical and, if not impossible, highly improbable under the circumstance that the ethical, legal, scientific, and social environment is not one that favors these goals. Nonetheless, responsible science and policy require that one concern for reviewers of stem cell research is to address the potential risks with experiments that involve the mixing of stem cells from two or more species. Clinical Trials: In the very near future, we are likely to see clinical trials based on reputable, pluripotent stem cell research. We are already seeing numerous stem cell "trials" worldwide that are arguably questionable, and sometimes criminal. By taking advantage of public awareness of and excitement about stem cell research, it is now possible to find groups that will offer to treat or cure almost anything in the context of a clinical "trial" that typically has no control group and for which participants must pay for participation. Payments for such "trials" are often on the order of $10,000 or more. Whether intentional or not, these trials are likely to be scams with little chance of success. Particularly under these circumstances, the stem cell field must meet a higher than average standard before approving the first clinical trials with this very new approach to treating disease. To do otherwise risks a backlash against all of stem cell research if initial trials unexpectedly result in a worsening of disease, serious side effects, or even death. All of these are possible outcomes no matter how much work has been done before the first trials in humans. Therefore to decrease that risk the scientific community can and should set a high bar both for the circumstances under which such a trial should be attempted and for the design of the research study to ensure the highest level of protections for informed consent and the welfare of the research participants.
• Obama BH (2009): Removing Barriers to Responsible Scientific Research Involving Human Stem Cells. Executive Order 13505 http://edocket.access.gpo.gov/2009/pdf/E9-5441.pdf
• NIH (2009): National Institutes of Health Guidelines on Human Stem Cell Research. http://stemcells.nih.gov/policy/pages/2009guidelines.aspx .
• NIH Human Embryonic Stem Cell Registry. http://grants.nih.gov/stem_cells/registry/current.htm
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MINI REVIEW article

This article is part of the research topic.

Muscle Stem Cells for Duchenne Muscular Dystrophy

Imaging Analysis for Muscle Stem Cells and Regeneration Provisionally Accepted

• 1 Greg Marzolf Jr. Muscular Dystrophy Center, Medical School, University of Minnesota, United States
• 2 Department of Neurology, Medical School, University of Minnesota, United States
• 3 Stem Cell Institute, Medical School, University of Minnesota, United States

The final, formatted version of the article will be published soon.

Composed of a diverse variety of cells, the skeletal muscle is one of the body's only tissues with the remarkable ability to regenerate after injury. One of the key players in the regeneration process is the muscle satellite cell (MuSC), a stem cell population for skeletal muscle, as it is the source of new myofibers. Maintaining MuSC quiescence during homeostasis involves complex interactions between MuSCs and other cells in their corresponding niche in adult skeletal muscle. After the injury, MuSCs are activated to enter the cell cycle for cell proliferation and differentiate into myotubes, followed by myofibers to regenerate muscle. Despite decades of research, the exact mechanisms underlying MuSC maintenance and activation remain elusive. Traditional methods of analyzing MuSCs, including cell cultures, animal models, and gene expression analyses, provide some insight into MuSC biology but lack the ability to replicate the 3-dimensional (3-D) in vivo muscle environment and capture dynamic processes comprehensively. Recent advancements in imaging technology, including confocal, intra-vital, and multiphoton microscopies, provide promising avenues for dynamic MuSC morphology and behavior to be observed and characterized. This chapter aims to review live-imaging methods that have contributed to uncovering insights into MuSC behavior, morphology changes, interactions within the muscle niche, and internal signaling pathways during the quiescence to activation (Q-A) transition. Integrating advanced imaging modalities and computational tools provides a new avenue for studying complex biological processes in skeletal muscle regeneration and muscle degenerative diseases such as sarcopenia and Duchenne muscular dystrophy (DMD).

Keywords: myogenesis, muscle stem cell, muscle regeneration, Duchenne muscular dystrophy, Satellite cell, Endothelial cell, skeletal muscle, niche

Received: 02 Apr 2024; Accepted: 15 Apr 2024.

Copyright: © 2024 Asakura and Karthikeyan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Atsushi Asakura, Greg Marzolf Jr. Muscular Dystrophy Center, Medical School, University of Minnesota, Minneapolis, Minnesota, United States

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Natalia Gomez-Ospina, MD, PhD

The assistant professor of pediatrics has been honored with the 2024 Dr. Michael S. Watson Innovation Award from the American College of Medical Genetics and Genomics. Gomez-Ospina was acknowledged for discovering several new genetic conditions and for her research to advance cell-based therapies for genetic disorders. Specifically, she was recognized for using genome editing to engineer hematopoietic stem cells to treat lysosomal storage diseases.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit http://mednews.stanford.edu .

2 hr 25 min

Why is This Gene Different from All other Genes? Genetics and Stem Cell Research in Jewish Law with Rabbi Dr. Edward Reichman Turn it and Turn it

This season of Turn it & Turn it is on the topic of: "Modern Medicine"  From pre-implantation genetic diagnosis to prenatal testing to disease markers for cancer, what are the halakhic ramifications of genetic and stem cell research? Topics include designer babies, the status of the human embryo in halakhah, and the rabbinic response to the latest technological advances in this exciting field. Click here to view the accompanying source sheet.  This audio was originally recorded on 12/27/2004 as part of Drisha's Winter Week. 

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Researchers identify protein that controls CAR T cell longevity

Foxo1 is required for memory in t cells and is associated with more durable clinical responses to car t cell therapy.

CAR T cell therapy has revolutionized the way certain types of cancer are treated, and the longer those CAR T cells live in a patient's body, the more effectively they respond to cancer. Now, in a new study, researchers at Children's Hospital of Philadelphia (CHOP) and Stanford Medicine have found that a protein called FOXO1 improves the survival and function of CAR T cells, which may lead to more effective CAR T cell therapies and could potentially expand its use in difficult-to-treat cancers. The findings were published online today by the journal Nature .

T cells are a type of immune cell that recognize and kill pathogens in order to protect the host. Cancer is often able to evade the body's immune system, but as a result of CAR T cell therapy, a patient's own T cells can be reprogrammed to recognize and kill these cancer cells, which has led to FDA-approved treatments for certain types of lymphomas and leukemias.

However, fewer than 50% of patients who receive CAR T cell therapy remain cured after a year. One of the reasons for this is that CAR T cells often don't survive long enough in patients to completely eradicate their cancer. Prior research has demonstrated that patients who are cured through CAR T cell therapy often have CAR T cells that live longer and can more successfully fight cancerous cells.

To determine what helps CAR T cells live longer, researchers wanted to understand the underlying biology behind memory T cells, which are a type of natural T cell whose purpose is to persist and retain function. One protein of interest, FOXO1, which activates genes associated with T cell memory, has previously been studied in mice but remains under-researched in human T cells or CAR T cells.

"By studying factors that drive memory in T cells, like FOXO1, we can enhance our understanding of why CAR T cells persist and work more effectively in some patients compared to others," said senior study author Evan Weber, PhD, an Assistant Professor of Pediatrics at the University of Pennsylvania Perelman School of Medicine and cell and gene therapy researcher within the CHOP Center for Childhood Cancer Research (CCCR) and the Center for Cellular and Molecular Therapeutics (CCMT).

To learn more about the role of FOXO1 in human CAR T cells, the researchers in this study used CRISPR to delete FOXO1. They found that in the absence of FOXO1, human CAR T cells lose their ability to form a healthy memory cell or protect against cancer in an animal model, supporting the notion that FOXO1 controls memory and antitumor activity.

Researchers then applied methods to force CAR T cells to overexpress FOXO1, which turned on memory genes and enhanced their ability to persist and fight cancer in animal models. In contrast, when the researchers overexpressed a different memory-promoting factor, there was no improvement in CAR T cell activity, suggesting that FOXO1 plays a more unique role in promoting T cell longevity.

Importantly, researchers also found evidence that FOXO1 activity in patient samples correlates with persistence and long-term disease control, thereby implicating FOXO1 in clinical CAR T cell responses.

"These findings may help improve the design of CAR T cell therapies and potentially benefit a wider range of patients," Weber said. "We are now collaborating with labs at CHOP to analyze CAR T cells from patients with exceptional persistence to identify other proteins like FOXO1 that could be leveraged to improve durability and therapeutic efficacy."

This study was supported by the National Cancer Institute Immunotherapy Discover and Development grants 1U01CA232361-A1, K08CA23188-01, U01CA260852, and U54CA232568-01; the National Human Genome Research Institute grant K99 HGHG012579 (C.A.L.); the Parker Institute for Cancer Immunotherapy; V Foundation for Cancer Research; Society for Immunotherapy of Cancer Rosenberg Scholar Award; Stand Up 2 Cancer -- St. Baldrick's -- NCI grant SU2CAACR-DT1113; and the Virginia and D.K. Ludwig Fund for Cancer Research and NCI grant U2C CA233285.

• Brain Tumor
• Lung Cancer
• Immune System
• Skin Cancer
• Prostate Cancer
• Adult stem cell
• Car accident
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• Embryonic stem cell
• Gene therapy
• Stem cell treatments

Story Source:

Materials provided by Children's Hospital of Philadelphia . Note: Content may be edited for style and length.

Journal Reference :

• Alexander E. Doan, Katherine P. Mueller, Andy Y. Chen, Geoffrey T. Rouin, Yingshi Chen, Bence Daniel, John Lattin, Martina Markovska, Brett Mozarsky, Jose Arias-Umana, Robert Hapke, In-Young Jung, Alice Wang, Peng Xu, Dorota Klysz, Gabrielle Zuern, Malek Bashti, Patrick J. Quinn, Zhuang Miao, Katalin Sandor, Wenxi Zhang, Gregory M. Chen, Faith Ryu, Meghan Logun, Junior Hall, Kai Tan, Stephan A. Grupp, Susan E. McClory, Caleb A. Lareau, Joseph A. Fraietta, Elena Sotillo, Ansuman T. Satpathy, Crystal L. Mackall, Evan W. Weber. FOXO1 is a master regulator of memory programming in CAR T cells . Nature , 2024; DOI: 10.1038/s41586-024-07300-8

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