Previous work has suggested that many stem cells can be found in microanatomic niches, where adjacent somatic cells of the niche control the differentiation and proliferation states of their resident stem cells. Recently published work examining intestinal stem cells (ISCs) in the adult Drosophila midgut suggests a new paradigm where some stem cells actively control the cell fate decisions of their daughters. Here, we review recent literature(1) demonstrating that, in the (...) absence of a detectable stem cell niche, multipotent Drosophila ISCs modulate the Notch signaling pathway in their adjacent daughter cells in order to specify the differentiated lineages of their descendants. These observations made in Drosophila are challenging and advancing our understanding of stem cell biology. BioEssays 30:107–109, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

This article considers the role of the adult epithelial stem cell, with particular reference to the intestinal epithelial stem cell. Although the potential of adult stem cells has been revealed in a number of recent publications, the organization and control of the stem cell hierarchy in epithelial tissues is still not fully understood. The intestinal epithelium is an excellent model in which to study such hierarchies, having a distinctive polarity and high rate of (...) cell proliferation and migration. Studies on the small intestinal crypt provide insight into the characteristics of the stem cells in normal and regenerating circumstances and demonstrate why a thorough understanding of these cells is an essential pre‐requisite for stem cell based therapeutic approaches. BioEssays 24:91–98, 2002. © 2002 John Wiley & Sons, Inc. (shrink)

Recently, Quyn et al. demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene (APC) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti‐tumourigenic (...) mechanism. We describe how hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se, with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers. (shrink)

The human intestines are constantly under the influence of numerous pathological factors: enteropathogenic microorganisms, food antigens, physico‐chemical stress associated with digestion and bacterial metabolism, therefore it must be provided with a system of protection against adverse impact. Recent studies have shown that Paneth cells play a crucial role in maintaining homeostasis of the small intestines. Paneth cells perform many vital functions aimed at maintaining a homeostatic balance between normal microbiota, infectious pathogens and the human body, regulate the qualitative (...) composition and number of intestinal microorganisms, prevent the introduction of potentially pathogenic species, and protect stem cells from damage. Paneth cells take part in adaptive and protective‐inflammatory reactions. Paneth cells maintain dynamic balance between microbial populations, and the macroorganism, preventing the development of intestinal infections and cancer. They play a crucial role in gastrointestinal homeostasis and may be key factors in the etiopathological progression of intestinal diseases. (shrink)

Unraveling molecular and functional heterogeneity of niche cells within the developing endoderm could resolve mechanisms of tissue formation and maturation. Here, we discuss current unknowns in molecular mechanisms underlying key developmental events in pancreatic islet and intestinal epithelial formation. Recent breakthroughs in single‐cell and spatial transcriptomics, paralleled with functional studies in vitro, reveal that specialized mesenchymal subtypes drive the formation and maturation of pancreatic endocrine cells and islets via local interactions with epithelium, neurons, and microvessels. Analogous to (...) this, distinct intestinal niche cells regulate both epithelial development and homeostasis throughout life. We propose how this knowledge can be used to progress research in the human context using pluripotent stem cell‐derived multilineage organoids. Overall, understanding the interactions between the multitude of microenvironmental cells and how they drive tissue development and function could help us make more therapeutically relevant in vitro models. (shrink)

It has recently been shown that stem and progenitor cells undergo population self‐renewal to maintain epithelial homeostasis. The fate of individual cells is stochastic but the production of proliferating and differentiating cells is balanced across the population. This new paradigm, originating in mouse epidermis and since extended to mouse oesophagus and mouse and Drosophila intestine, is in contrast to the long held model of epithelial maintenance by exclusively asymmetric division of stem cells. Recent lineage (...) tracing studies have now shown that wound responses vary between tissues, and that a stem cell reserve is not essential as cycling progenitors and even differentiating cells contribute to regeneration. (shrink)

Examining stem cell biology from a philosophy of science perspective, this book clarifies the field's central concept, the stem cell, as well as its aims, methods, models, explanations and evidential challenges. The first chapters discuss what stem cells are, how experiments identify them, and why these two issues cannot be completely separated. The basic concepts, methods and structure of the field are set out, as well as key limitations and challenges. The second part of the book (...) shows how rigorous explanations emerge from stem cell experiments, and compares these to other kinds of scientific explanation. Model organisms, the role of genes, and the significance of collaboration are also discussed. The last part of the book considers relations to systems biology and clinical medicine, arguing that both the mathematical models of the former, and ethical principles of the latter, are necessary for stem cell biology to deliver on its promises. (shrink)

“Stem Cells Dependently Arising and Empty” May 2021, Buddhism and Culture (a Korean-language Buddhist magazine sponsored by the Foundation for the Promotion of Korean Buddhism), Korea.

In this paper the permissibility of stem cell research on early human embryos is defended. It is argued that, in order to have moral status, an individual must have an interest in its own wellbeing. Sentience is a prerequisite for having an interest in avoiding pain, and personhood is a prerequisite for having an interest in the continuation of one's own existence. Early human embryos are not sentient and therefore they are not recipients of direct moral consideration. Early human (...) embryos do not satisfy the requirements for personhood, but there are arguments to the effect that they should be treated as persons nonetheless. These are the arguments from potentiality, symbolic value and the principle of human dignity. These arguments are challenged in this paper and it is claimed that they offer us no good reason to believe that early human embryos should be treated as persons. (shrink)

While the clinical promise of much stem cell research remains largely theoretical, patients are nonetheless pursuing unproven stem cell therapies in jurisdictions around the world—a phenomenon referred to as “stem cell tourism.” These treatments are generally advertised on a direct-to-consumer basis via the Internet. Research shows portrayals of stem cell medicine on such websites are overly optimistic and the claims made are unsubstantiated by published evidence. However, anecdotal evidence suggests that parents are pursing these “treatments” for (...) their children, despite potential physical and financial risk. Physicians are in a unique position as they can be expected to be involved in, or privy to, such decisions. In this paper, we consider what duties physicians may have toward minor patients whose parents/guardians wish to engage in stem cell tourism on their behalf. We use the Canadian perspective to address the broadly relevant issues raised by this trend. (shrink)

A new therapeutic strategy could break the stalemate in the war on cancer by targeting not all cancerous cells but the small fraction that lie at the root of cancers. Lucie Laplane offers a comprehensive analysis of cancer stem cell theory, based on an original interdisciplinary approach that combines biology, biomedical history, and philosophy.

If stem cell-based therapies are developed, we will likely confront a difficult problem of justice: for biological reasons alone, the new therapies might benefit only a limited range of patients. In fact, they might benefit primarily white Americans, thereby exacerbating long-standing differences in health and health care.

Now that stem cell scientists are clamouring for human eggs for cloning-based stem cell research, there is vigorous debate about the ethics of paying women for their eggs. Generally speaking, some claim that women should be paid a fair wage for their reproductive labour or tissues, while others argue against the further commodification of reproductive labour or tissues and worry about voluntariness among potential egg providers. Siding mainly with those who believe that women should be financially compensated for (...) providing eggs for research, the new stem cell guidelines of the International Society for Stem Cell Research (ISSCR) legitimise both reimbursement of direct expenses and financial compensation for many women who supply eggs for research. In this paper, the authors do not attempt to resolve the thorny issue of whether payment for eggs used in human embryonic stem cell research is ethically legitimate. Rather, they want to show specifically that the ISSCR recommended payment practices are deeply flawed and, more generally, that all payment schemes that aim to avoid undue inducement of women risk the global exploitation of economically disadvantaged women. (shrink)

Recent advances in stem cell research suggest that in the future it may be possible to create eggs and sperm from human stem cells through a process that we term in vitro gametogenesis (IVG). IVG would allow treatment of some currently untreatable forms of infertility. It may also allow same-sex couples to have genetically-related children. For example, cells taken from one man could potentially be used to create an egg, which could then be fertilised using naturally (...) produced sperm from another man to create a genetically-related child with half of its DNA from each of the men. In this chapter, we consider whether this technology could justifiably be denied to same-sex couples if it were made available as a fertility treatment to different-sex couples. We argue that it could not. (shrink)

This paper examines a case of failed interdisciplinary collaboration, between experimental stem cell research and theoretical systems biology. Recently, two groups of theoretical biologists have proposed dynamical systems models as a basis for understanding stem cells and their distinctive capacities. Experimental stem cell biologists, whose work focuses on manipulation of concrete cells, tissues and organisms, have largely ignored these proposals. I argue that ‘failure to communicate’ in this case is rooted in divergent views of explanation: (...) the theoretically-inclined modelers are committed to a version of the covering-law view, while experimental stem cell biologists aim at mechanistic explanations. I propose a way to reconcile these two explanatory approaches to cell development, and discuss the significance of this result for interdisciplinary collaboration in systems biology and beyond. (shrink)

Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases) ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the (...) lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial) characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells. (shrink)

This article examines the assertion that human embryonic stem cells patents are immoral because they violate human dignity. After analyzing the concept of human dignity and its role in bioethics debates, this article argues that patents on human embryos or totipotent embryonic stem cells violate human dignity, but that patents on pluripotent or multipotent stem cells do not. Since patents on pluripotent or multipotent stem cells may still threaten human dignity by encouraging (...) people to treat embryos as property, patent agencies should carefully monitor and control these patents to ensure that patents are not inadvertently awarded on embryos or totipotent stem cells. (shrink)

Research using human embryonic stem cells raises an array of complex ethical issues, including, but by no means limited to, the moral status of developing human life. Unfortunately much of the public discussion fails to take into account this complexity. Advocacy for liberal and conservative positions on human embryonic stem cell research can be simplistic and misleading. Ethical concepts such as truth-telling, scientific integrity, and social justice should be part of the debate over federal support for human (...) embryonic stem cell research. Moreover, the debate should be conducted in accord with principles of deliberative democracy, including respect for people holding competing views. (shrink)

Policy arguments in support of stem cell research often use economic benefit as a key rationale for permissive policies and increased government funding. Economic growth, job creation, improved productivity, and a reduction in the burden of disease are all worthy goals and, as such, can be used as powerful rhetorical tools in efforts to sway voters, politicians, and funding agencies. However, declarations of economic and commercial benefit — which can be found in policy reports, the scientific literature, public funding (...) policies, and the popular press — have arguably created a great deal of expectation. Can stem cell research deliver on the economic promise? And what are the implications of this economic ethos for the researchers who must work under its shadow? (shrink)

Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to cancer. (...) Despite being still far from becoming a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment. (shrink)

Understanding aging and how it affects an organism's lifespan is a fundamental problem in biology. A hallmark of aging is stem cell senescence, the decline of functionality, and number of somatic stem cells, resulting in an impaired regenerative capacity and reduced tissue function. In addition, aging is characterized by profound remodeling of the immune system and a quantitative decline of adequate immune responses, a phenomenon referred to as immune‐senescence. Yet, what is causing stem cell and immune‐senescence? (...) This review discusses experimental studies of potentially immortal Hydra which have made contributions to answering this question. Hydra transcription factor FoxO has been shown to modulate both stem cell proliferation and innate immunity, lending strong support to a role of FoxO as critical rate‐of‐aging regulator from Hydra to human. Constructing a model of how FoxO responds to diverse environmental factors provides a framework for how stem cell factors might contribute to aging. (shrink)

Stem cell tourism is a small but growing part of the thriving global medical tourism marketplace. Much stem cell research remains at the experimental stage, with clinical trials still uncommon. However, there are over 700 clinics estimated to be operating in mostly developing countries – from Costa Rica and Argentina to China, India and Russia – that have lured many patients, mostly from industrialized countries, driven by desperation and hope, which in turn continue to fuel the growth of (...) such tourism.While much research has focused on such dimensions as the promotions that allow such businesses to make their services known, media coverage, some patient research, and regulatory conditions for developing country clinics, little attention has been paid to the non-affected members of the general population, the future potential users of such services. This empirical study based on five focus group discussions with a diverse group of healthy adults in a Canadian city, explored participant views of patients who use stem cell tourism services, the likelihood they would avail themselves of such services if they were to suffer similar illnesses, and the conditions under which they might do so, and the impact that admonitions and advice from international expert bodies might have on their decisions. Our findings suggest that these healthy adults are sympathetic to the drivers of hope and desperation, and, despite cautions about research limitations, may seek such treatments themselves under similar conditions. These findings are discussed in the context of the policy and ethical issues raised by this form of medical tourism. (shrink)

The research on stem cell-based therapies has greatly expanded in recent years. Our text attempts to seek those religious and ethical challenges that stem cell therapy and research bring into debate. Our thesis is that bioethics can defend its principle without a religious background. We will develop our argumentation on three major points: firstly, a comparison between secular ethics and religious views will clarify why stem cell therapy and research are important from a scientific point of view, (...) addressing the very center of the human being; in our view, being based on secular society, bioethics can answer the challenges of stem cell therapy and research; secondly, following Hans Jonas' perspective on experimenting on humans, we seek to understand the philosophical guidance that sciences dealing with stem cell need; thirdly, we will map the ethical guidelines for clinical translational research that have been adopted by the International Society for Stem Cell Research. . (shrink)

Endosteal stem cells are a subclass of bone marrow skeletal stem cell populations that are particularly important for rapid bone formation occurring in growth and regeneration. These stem cells are strategically located near the bone surface in a specialized microenvironment of the endosteal niche. These stem cells are abundant in young stages but eventually depleted and replaced by other stem cell types residing in a non‐endosteal perisinusoidal niche. Single‐cell molecular profiling and in (...) vivo cell lineage analyses play key roles in discovering endosteal stem cells. Importantly, endosteal stem cells can transform into bone tumor‐making cells when deleterious mutations occur in tumor suppressor genes. The emerging hypothesis is that osteoblast‐chondrocyte transitional identities confer a special subset of endosteal stromal cells with stem cell‐like properties, which may make them susceptible for tumorigenic transformation. Endosteal stem cells are likely to represent an important therapeutic target of bone diseases caused by aberrant bone formation. (shrink)

The pursuit of unproven stem cell-based interventions is an emerging issue that raises various concerns. Physicians play different roles in this market, many of which engage their legal, ethical and professional obligations. In Canada, physicians are members of a self-regulated profession and their professional regulatory bodies are responsible for regulating the practice of medicine and protecting the public interest. They also provide policy guidance to their members and discipline members for unprofessional conduct.

Robert Sparrow has recently raised the possibility that stem cell technology could in the future be used to create multiple generations of embryos in the laboratory before transferring one embryo to a woman’s womb to create a pregnancy. Sparrow argues that any children produced in this way would be genetic orphans—they would lack living genetic parents—and explores the possible moral implications of this. A number of other authors have raised objections to Sparrow’s moral claims, but his descriptive claim remains (...) unchallenged. In this chapter, we challenge it, arguing that Sparrow’s imagined technology could be performed in such a way that the children produced would have living genetic parents. (shrink)

Embryonic stem cell research has been a source of ethical, legal, and social controversy since the first successful culturing of human ESCs in the laboratory in 1998. The controversy has slowed the pace of stem cell science and shaped many aspects of its subsequent development. This paper assesses the main issues that have bedeviled stem cell progress and identifies the ethical fault lines that are likely to continue.The time is appropriate for such an assessment because the field (...) is poised for a period of rapid development. President Obama has removed the Bush administration’s restrictions on federal funding. A huge influx of federal research funds is in the offing and presumably a more rapid maturing of the science will take place. Stem cell science is also moving into the clinical realm. In March 2009, the Food and Drug Administration approved the first clinical trial with an ESC-derived therapy for spinal cord injuries, an important first step — though by no means a final or a sure one — in moving ESC research out of the laboratory into clinical medicine. Finally, recent work with induced pluripotent stem cells suggests that non-embryonic sources of pluripotent stem cells may one day be routinely available. Such a development will lessen the temperature of the ethical debate while raising other issues. (shrink)

Skeletal muscle stem cells or satellite cells are responsible for muscle regeneration in the adult. Although satellite cells are highly resistant to stress, and display greater capacity to repair molecular damage than the committed progeny, their regenerative potential declines with age. During ageing, satellite cells switch to a state of permanent cell cycle arrest or senescence which prevents their activation. A recent study reveals that the senescence of satellite cell relies on defective autophagy, the quality (...) control mechanism that degrades damaged proteins and organelles. Molecular damage is generated by oxidative stress that also promotes epigenetic changes that activate the expression of master genes, in a double‐hit mechanism that ensures senescence. Importantly, genetic, and pharmacological correction of defective autophagy reverses satellite cell senescence and restores muscle regeneration in geriatric mice, with perspectives of modulating age‐related functional decline of muscle. This study provides new clues to understand stem cell and organismal ageing. (shrink)

Hematopoietic stem cell transplantation is a widely accepted practice in the United Kingdom (UK). The relatively liberal UK law permits donation both within families and from strangers, and even allows the creation of “saviour siblings” who are brought into being with the specific intent of having them donate stem cells to save other members of their family. This chapter describes the regulation of HSCT in the UK and highlights some ethical issues related to discrimination against some categories (...) of potential donors, the accuracy of the information provided to potential donors, and the controversy concerning saviour siblings. (shrink)

This essay will address the ethical issues that have emerged in the first considerations of the newly emerging stem cell technology. Many of us in the field of bioethics were deliberating related issues as we first learned of the new science and confronted the ethical issues it raised. In this essay, I will draw on the work of colleagues who were asked to reflect on early stages of the research as the field debated the issues of consent, moral status, (...) use of animal tissues, abortion, use of fetal tissue, and the nature and goals of entrepreneurial research. In this new capacity, ethicists weighed the problem of privacy, the role of justice considerations, and the issues of the marketplace in science. At this point, it is clear that far more issues remain unresolved than are settled, that there is largely unexplored territory ahead, and that the single most important task that faces us as a field is a steady call for ongoing conversation and public debate. (shrink)

Stem cells are defined as having capacities for both self-renewal and differentiation. Many different entities satisfy this working definition. I show that this general stem cell concept is relative to a cell lineage, temporal duration, and characters of interest. Experiments specify values for these variables. So claims about stem cells must be understood in terms of experimental methods used to identify them. Furthermore, the stem cell concept imposes evidential constraints on interpretation of experimental results. (...) From these constraints, it follows that claims about stem cell capacities are inherently uncertain. This result has important implications for stem cell research. (shrink)

Self‐renewal and differentiation of stem cells are tightly regulated processes subject to intrinsic and extrinsic signals. Molecular chaperones and co‐chaperones, especially heat shock proteins (Hsp), are ubiquitous molecules involved in the modulation of protein conformational and complexation states. The function of Hsp, which are typically associated with stress response and tolerance, is well characterized in differentiated cells, while their role in stem cells remains unclear. It appears that embryonic stem cells exhibit increased stress (...) tolerance and concomitant high levels of chaperone expression. This review critically evaluates stem cell research from a molecular chaperone perspective. Furthermore, we propose a model of chaperone‐modulated self‐renewal in mouse embryonic stem cells. (shrink)

This paper explores the notions of hope and how individual patient autonomy can trump carefully reasoned ethical concerns and policies intended to regulate stem cell transplants. We argue that the same limits of knowledge that inform arguments to restrain and regulate unproven treatments might also undermine our ability to comprehensively dismiss or condemn them. Incautiously or indiscriminately reasoned policies and attitudes may drive critical information and data underground, impel patients away from working with clinical researchers, and tread needlessly on (...) hope, the essential motivator of patients, advocates and researchers alike. We offer recommendations to clinicians and health care providers to help balance the discourse with individuals seeking treatment while guarding against fraud, misconception, and patient harm. (shrink)

This paper explores the notions of hope and how individual patient autonomy can trump carefully reasoned ethical concerns and policies intended to regulate stem cell transplants. We argue that the same limits of knowledge that inform arguments to restrain and regulate unproven treatments might also undermine our ability to comprehensively dismiss or condemn them. Incautiously or indiscriminately reasoned policies and attitudes may drive critical information and data underground, impel patients away from working with clinical researchers, and tread needlessly on (...) hope, the essential motivator of patients, advocates and researchers alike. We offer recommendations to clinicians and health care providers to help balance the discourse with individuals seeking treatment while guarding against fraud, misconception, and patient harm. (shrink)

Stem cell tourism is a small but growing part of the thriving global medical tourism marketplace. Much stem cell research remains at the experimental stage, with clinical trials still uncommon. However, there are over 700 clinics estimated to be operating in mostly developing countries – from Costa Rica and Argentina to China, India and Russia – that have lured many patients, mostly from industrialized countries, driven by desperation and hope, which in turn continue to fuel the growth of (...) such tourism.While much research has focused on such dimensions as the promotions that allow such businesses to make their services known, media coverage, some patient research, and regulatory conditions for developing country clinics, little attention has been paid to the non‐affected members of the general population, the future potential users of such services. This empirical study based on five focus group discussions with a diverse group of healthy adults in a Canadian city, explored participant views of patients who use stem cell tourism services, the likelihood they would avail themselves of such services if they were to suffer similar illnesses, and the conditions under which they might do so, and the impact that admonitions and advice from international expert bodies might have on their decisions. Our findings suggest that these healthy adults are sympathetic to the drivers of hope and desperation, and, despite cautions about research limitations, may seek such treatments themselves under similar conditions. These findings are discussed in the context of the policy and ethical issues raised by this form of medical tourism. (shrink)

In the context of stem cell research, the promise of economic growth has become a common policy argument for adoption of permissive policies and increased government funding. However, declarations of economic and commercial benefit, which can be found in policy reports, the scientific literature, public funding policies, and the popular press, have arguably created a great deal of expectation. Can stem cell research deliver on the economic promise? And what are the implications of this economic ethos for the (...) researchers who must work under its shadow? (shrink)

Sex is not the answer to everything, though young men think it is, but it may be the answer to the intractable debate over the ethics of human embryonic stem cell research. In this paper, I advance one ethical principle that, as yet, has not received the attention its platitudinous character would seem to merit. If found acceptable, this principle would permit the beneficial use of any embryonic or fetal tissue that would, by default, be lost or destroyed. More (...) important, I make two appeals to consistency, or to parity of reasoning, that I believe show that no one who either has used or intends to use sexual reproduction as their means of procreation, nor indeed anyone who has unprotected heterosexual intercourse, nor anyone who finds in vitro fertilization acceptable, nor anyone who believes that abortion is ever permissible can consistently object on principle to human embryo research nor to the use of embryonic stem cells for research or therapy. (shrink)

Controversy often follows when patents are obtained in a pioneering area of technology. Patent filing activity in the field of regenerative medicine and in relation to stem cells in particular has not escaped opprobrium, although it is instructive to compare the nature of the debates that are taking place over the patenting of stem cells in the US and Europe. In the US, debate over the early patent applications made by the Wisconsin Alumni Research Foundation has (...) been intense2, but at least it appears to have been grounded firmly in patent law principles. In Europe, the debate has skewed away from the basic patent law tenets of novelty, inventiveness and industrial utility and has entered something of a twilight zone, with the European Patent Office serving as a diffident forum for difficult moral and ethical arguments about the destruction of human embryos and the commercial exploitation of human life. (shrink)

The stem cell story is not a simple story but a complex narrative: one that requires careful analysis in order to identify major themes and plots. This paper offers an analysis of the ethics of the clinical application of stem cells and argues that even quite risky therapies can be ethical. These arguments cannot be used to justify all aspects of contemporary stem cell science, including human embryonic stem cell science, which remains theoretical and speculative. (...) It is argued that the homogenisation of stem cell science obscures the distinction between clinical application and experimental laboratory science in a morally problematic way. (shrink)

I argue that embryonic stem cell research is fair to the embryo, even on the assumption that the embryo has attained full personhood and an attendant right to life at conception. This is because the only feasible alternatives open to the embryo are to exist briefly in an unconscious state and be killed or to not exist at all. Hence, one is neither depriving the embryo of an enduring life it would otherwise have had nor is one causing the (...) embryo pain. I also argue that a rational agent in a situation relevantly similar to that of the embryo would consent to such research, and I use this insight to ground two justice-based arguments in favor of this research. (shrink)

Adult stem cell populations must coordinate their own maintenance with the generation of differentiated cell types to sustain organ physiology, in a spatially controlled manner and over long periods. Quantitative analyses of clonal dynamics have revealed that, in epithelia, homeostasis is achieved at the population rather than at the single stem cell level, suggesting that feedback mechanisms coordinate stem cell maintenance and progeny generation. In the central nervous system, however, little is known of the possible community processes (...) underlying neural stem cell maintenance. Recent work, in part based on intravital imaging made possible in the adult zebrafish, conclusively highlights that homeostasis in neural stem cell pools may rely on population asymmetry and long‐term spatiotemporal coordination of neural stem cell states and fates. These results suggest that neural stem cell assemblies in the vertebrate brain behave as self‐organized systems, such that the stem cells themselves generate their own intrinsic niche. (shrink)

In 1998, researchers established the first human embryonic stem cell line. Their scientific triumph triggered an ethics and policy argument that persists today. Bioethicists, religious leaders, government officials, patient advocates, and scientists continue to debate whether this research poses a promise, a threat, or a mixed ethical picture for society.Scientists are understandably excited about the knowledge that could come from studying human embryonic stem cells. Most of them believe these cells offer a precious opportunity to learn (...) more about why diseases develop and how they might be prevented or attacked. In their quest to gain support for stem cell research, scientists and others have claimed that the research could generate cures and treatment for everything from heart disease to cancer. (shrink)

BackgroundIn 2004, patient advocate groups were major players in helping pass and implement significant public policy and funding initiatives in stem cells and regenerative medicine. In the following years, advocates were also actively engaged in Washington DC, encouraging policy makers to broaden embryonic stem cell research funding, which was ultimately passed after President Barack Obama came into office. Many advocates did this because they were told stem cell research would lead to cures. After waiting more than (...) 10 years, many of these same patients are now approaching clinics around the world offering experimental stem cell-based interventions instead of waiting for scientists in the US to complete clinical trials. How did the same groups who were once the strongest supporters of stem cell research become stem cell tourists? And how can scientists, clinicians, and regulators work to bring stem cell patients back home to the US and into the clinical trial process?DiscussionIn this paper, we argue that the continued marketing and use of experimental stem cell-based interventions is problematic and unsustainable. Central problems include the lack of patient protection, US liability standards, regulation of clinical sites, and clinician licensing. These interventions have insufficient evidence of safety and efficacy; patients may be wasting money and time, and they may be forgoing other opportunities for an intervention that has not been shown to be safe and effective. Current practices do not contribute to scientific progress because the data from the procedures are unsuitable for follow-up research to measure outcomes. In addition, there is no assurance for patients that they are receiving the interventions promised or of what dosage they are receiving. Furthermore, there is inconsistent or non-existent follow-up care. Public policy should be developed to correct the current situation.ConclusionThe current landscape of stem cell tourism should prompt a re-evaluation of current approaches to study cell-based interventions with respect to the design, initiation, and conduct of US clinical trials. Stakeholders, including scientists, clinicians, regulators and patient advocates, need to work together to find a compromise to keep patients in the US and within the clinical trial process. Using HIV/AIDS and breast cancer advocate cases as examples, we identify key priorities and goals for this policy effort. (shrink)

This overview of 10 years of stem cell controversy reviews the moral conflict that has made ESCs so controversial and how this conflict plays itself out in the legal realm, focusing on the constitutional status of efforts to ban ESC research or ESC-derived therapies. It provides a history of the federal funding debate from the Carter to the Obama administrations, and the importance of the Raab memo in authorizing federal funding for research with privately derived ESCs despite the Dickey-Wicker (...) ban on federal funding of embryo research. It also reviews the role that scientists themselves have played in developing regulations for ESC research, the emergence of ESCROs as special review bodies for ESC research, and the thorough consent requirements for donation of IVF embryos to ESC research. With research now transitioning from the lab to the clinic, the article reviews the challenges of ensuring safety and consent in translational research. It concludes with a call for respecting those persons who have to using or working with ESC products and an account of how obtaining stem cells from a person's own cells will alleviate some but not all of the controversy surrounding ESC research. (shrink)

Stem cells have the capacity both to self‐renew and to give rise to differentiated progeny, and are vital to the organization of multicellular organisms. Stem cells raise a number of fundamental questions regarding lineage restriction and cellular differentiation, and they hold enormous promise for cell‐based therapies. Here I propose a theoretical framework for stem cell biology based on the concepts of autopoiesis (self‐production) and complementarity. I argue that stem cells are pivotal in the (...) self‐production of the organism and that we need complementary approaches to understand their probabilistic behavior. I discuss how this framework generates testable hypotheses regarding stem‐cell functions. BioEssays 26:1013‐1016, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

This article examines a moral problem for the blastocyst transfer method of harvesting stem cells from embryos. Although BTM does not result in the destruction of an embryo, this article suggests that BTM nevertheless faces difficulty because it poses a threat to the autonomy of the embryo.

This article contributes to the current debate on human embryonic stem cell researchers’ possible complicity in the destruction of human embryos and the relevance of such complicity for the issue of commodification of human embryos. I will discuss if, and to what extent, researchers who destroy human embryos, and researchers who merely use human embryos destroyed by others, have moral use rights, and/or moral property rights, in these embryos. I argue that the moral status of the human embryo, however (...) justified, places few restrictions on the latter researchers’ use of it, and property rights in it, once it is destroyed. I argue that the former researchers have no property rights in the destroyed embryo but use rights in it to the extent allowed by the legitimate owners of the destroyed embryo. I discuss the implications of this account for previous and current US federal law regulating human embryonic stem cell research. (shrink)

Debate on the potential and uses of human stem cells tends to be conducted by two constituencies—ethicists and scientists. On many occasions there is little communication between the two, with the result that ethical debate is not informed as well as it might be by scientific insights. The aim of this paper is to highlight those scientific insights that may be of relevance for ethical debate.Environmental factors play a significant role in identifying stem cells and their (...) various subtypes. Research related to the role of the microenvironment has led to emphasis upon “plasticity”, which denotes the ability of one type of stem cell to undergo a transition to cells from other lineages. This could increase the value given to adult stem cells, in comparison with embryonic stem cell research. Any such conclusion should be treated with caution, however, since optimism of this order is not borne out by current research.The role of the environment is also important in distinguishing between the terms totipotency and pluripotency. We argue that blastocysts and embryonic stem cells are only totipotent if they can develop within an appropriate environment. In the absence of this, they are merely pluripotent. Hence, blastocysts in the laboratory are potentially totipotent, in contrast to their counterparts within the human body which are actually totipotent. This may have implications for ethical debate, suggesting as it does that arguments based on potential for life may be of limited relevance. (shrink)

What is a stem cell? The answer is seemingly obvious: a cell that is also a stem, or point of origin, for something else. Upon closer examination, however, this combination of ideas leads directly to fundamental questions about biological development. A cell is a basic category of living thing; a fundamental 'unit of life.' A stem is a site of growth; an active source that supports or gives rise to something else. Both concepts are deeply rooted in (...) biological thought, with rich and complex histories. The idea of a stem cell unites them, but the union is neither simple nor straightforward. This book traces the origins of the stem cell concept, its use in stem cell research today, and implications of the idea for stem cell experiments, their concrete results, and hoped-for clinical advances. (shrink)

It has been suggested that future application of stem-cell derived gametes might lead to the possibility for same-sex couples to have genetically related children. Still, for this to become possible, the technique of gamete derivation and techniques of reprogramming somatic cells to a pluripotent state would have to be perfected. Moreover, egg cells would have to be derived from male cells and sperm cells from female cells, which is believed to be particularly difficult, if (...) not impossible. We suggest a more plausible scenario to provide same-sex couples with the possibility to parent a child who is genetically related to both parents. Although technical feasibility is an advantage, disadvantages are that cooperation of a donor of the opposite sex is still required and that the partners are genetically linked to the resulting child in a different degree. However, since in our scenario the donor's genetic contribution would not outweigh any of the parents' genetic contribution, this alternative route may ease the fear for a possible parental claim by the donor. Like many other applications in the field of infertility treatment, the goal to create SCD-gametes for reproductive purposes is largely based on the high value attributed to genetic parenthood. Although we believe that genetic relatedness is neither a necessary nor a sufficient condition for ‘good’ parenthood, we do believe that many people may consider our scenario a welcome alternative. (shrink)