Cellular mechanisms whereby quiescent stem cells sense tissue injury and transition to an activated state are largely unknown. Quiescent skeletal muscle stem cells (MuSCs, also called satellite cells) have elaborate, heterogeneous projections that rapidly retract in response to muscle injury. They may therefore act as direct sensors of their niche environment. Retraction is driven by a Rac‐to‐Rho GTPase activity switch that promotes downstream MuSC activation events. These and other observations lead to several hypotheses: (1) projections are (...) morphologically dynamic at quiescence, providing a surveillance function for muscle damage; (2) quiescent projection dynamics are regulated by the relative balance of Rac and Rho activities promoted by niche‐derived cues; (3) projections, particularly their associated filopodia, sense tissue damage via changes to the biomechanical properties of the niche and/or detection of signaling cues released by damaged myofibers; and (4) the dynamic nature of projections results in a population of MuSCs with heterogeneous functional properties. These concepts may extend to other types of quiescent stem cells, as well as prove useful in translational research settings. (shrink)

Cell‐based therapies for degenerative diseases of the musculature remain on the verge of feasibility. Myogenic cells are relatively abundant, accessible, and typically harbor significant proliferative potential ex vivo. However, their use for therapeutic intervention is limited due to several critical aspects of their complex biology. Recent insights based on mouse models have advanced our understanding of the molecular mechanisms controlling the function of myogenic progenitors significantly. Moreover, the discovery of atypical myogenic cell types with the ability to cross (...) the blood‐muscle barrier has opened exciting new therapeutic avenues. In this paper, we outline the major problems that are currently associated with the manipulation of myogenic cells and discuss promising strategies to overcome these obstacles. (shrink)

I investigate the intrinsic/extrinsic nature of stemness in muscle stem cells (MSC) by relying on recent research on quiescence, with the aim of shedding light on the nature of dispositions and deriving some consequences about stem cells. First, I argue why the study of quiescence is the best available way to establish any claim about the intrinsicness/extrinsicness of stemness at least is some stem cells. Drawing on that, I argue that MSC’s stem capacities result from (...) the combination of intrinsic cues plus extrinsic factors from the stem cell niche, making stemness an extrinsic disposition in MSC. Importantly, it is shown that the niche allows the instantiation of stemness in MSC by acting as a masker of its manifestation. This shows that stemness is, at least in MSC, what I call an extrinsically structurally masked disposition (SMD); that is, a disposition whose instantiation requires, as a condition of possibility, the interaction between the bearer and a masker. Finally, I conclude by suggesting some potential consequences of this observation for the philosophical study of dispositions and for stem cell research. (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)

In recent years, live imaging has been adopted to study stem cells in their native environment at cellular resolution. In the skeletal muscle field, this has led to visualising the initial events of muscle repair in mouse, and the entire regenerative response in zebrafish. Here, we review recent discoveries in this field obtained from live imaging studies. Tracking of tissue resident stem cells, the satellite cells, following injury has captured the morphogenetic dynamics of stem/progenitor cells (...) as they facilitate repair. Asymmetric satellite cell division generated a clonogenic progenitor pool, providing in vivo validation for this mechanism. Furthermore, there is an emerging role of stem/progenitor cell guidance at the injury site by cellular protrusions. This review concludes that live imaging is a critical tool for discovering the distinct processes that occur during regeneration, emphasising the importance of imaging in diverse animal models to capture the entire scope of stem cell functions. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 97-114 [Access article in PDF] Stem Cell Research in the U.S. after the President's Speech of August 2001 Cynthia B. Cohen On 9 August 2001, in a nationally televised speech, President Bush addressed the contentious question of whether to provide federal funds for human embryonic stem cell research (White House 2001).1 This research involves taking the primordial cells (...) found in embryos and transforming them into certain specialized cells, such as those of the heart, nerves, and muscles, with the ultimate goal of transferring these cells into patients to repair damaged cells and tissues. In his remarks, the President authorized funding for research only on stem cells already harvested from remaining embryos at in vitro fertilization (IVF) centers as of 9 August 2001, the date of the speech. In a "Fact Sheet" about embryonic stem cell research, he added the ethical requirements that (1) the donors of embryos gave informed consent to the derivation of stem cells from their embryos, (2) the embryos were created solely for reproductive purposes, and (3) no financial inducements were given to the embryo donors. The President also prohibited federally funded research on embryonic stem cells derived from embryos after 9 August 2001, as well as the creation of embryos for research purposes and the cloning of human embryos for both reproductive and research purposes. He did not seek to ban the pursuit of embryonic stem cell research with private funds. "This allows us to explore the promise and potential of stem-cell research without crossing a fundamental moral line by providing taxpayer funding that would sanction or encourage further destruction of embryos," the President stated (White House 2001).The President's speech stirred intense controversy. Many applauded the new policy because it allowed some embryonic stem cell research to proceed, thereby raising hope that treatments might be developed for those suffering from such conditions as Parkinson's disease, Alzheimer's disease, and diabetes. Others supported it on grounds that it would discourage the future destruction of embryos in stem cell research. They maintained that although it was wrong to have derived stem cells from embryos, this wrong was no longer remediable and it therefore was justifiable to allow research using such embryos to proceed. Some, however, objected to the new policy because they held that it unduly limited the [End Page 97] number of embryonic stem cells available for federally funded research. Still others opposed it on grounds that it made the federal government complicit in what they took to be the wrongful destruction of human embryos that had taken place prior to 9 August 2001. The President established the President's Council on Bioethics by executive order in November 2001 and charged it, among other tasks, with monitoring stem cell research and recommending guidelines and regulations for biomedical innovations.Questions about the moral status of human embryos have so captured public attention since the President issued his remarks that other significant ethical and policy issues raised about stem cell research inside the Beltway have remained in the shadows. A number of individuals and organizations—legislators, scientists, patient groups, the President's Council on Bioethics, ethicists, religious task forces, and social commentators—have attempted to bring these other issues to legislative and public attention. They also have revisited the more publicly prominent question of what sorts of protections we owe to human embryos. In response, Congress has attempted to address several of these newly emerging issues at hearings and in legislation. I review these efforts, consider developing issues and arguments, and conclude by exploring possible future directions for federal and private sector stem cell policy. The Availability of Embryonic Stem Cell Lines to Federally Funded Researchers President Bush, in developing his stem cell research policy, accepted a distinction between the "derivation" and the "use" of embryos enunciated by the General Counsel of the Department of Health and Human Services toward the end of the Clinton administration. This distinction was adopted to avoid contravening the Dickey-Wicker Amendment (added... (shrink)

Stem cell biology is driven by experiment. Its major achievements are striking experimental productions: "immortal" human cell lines from spare embryos (Thomson et al. 1998); embryo-like cells from "reprogrammed" adult skin cells (Takahashi and Yamanaka 2006); muscle, blood and nerve tissue generated from stem cells in culture (Lanza et al. 2009, and references therein). Well-confirmed theories are not so prominent, though stem cell biologists do propose and test hypotheses at a profligate rate. 1 (...) This paper aims to characterize the role of experiment in stem cell biology, so as to answer the following question: how do experiments contribute to our knowledge of stem cells and related phenomena? The .. (shrink)

Cells in the basal metazoan phylum Cnidaria are characterized by remarkable plasticity in their differentiation capacity. The mechanism controlling asymmetric cell divisions is not understood in cnidarians or in any other animal group. PIWI proteins recently have been shown to be involved in maintaining the self‐renewal capacity of stem cells in organisms as diverse as ciliates, flies, worms and mammals. Seipel et al.1 find that, in the cnidarian Podocoryne carnea, the Piwi homolog Cniwi is transcriptionally upregulated when the (...) polyp generates buds, which will develop into medusae. Since transdifferentiation of striated muscle cells to smooth muscle cells also activated Cniwi expression, Cniwi appears to play a crucial role in differentiation events. The discovery should facilitate elucidation of the poorly understood factors that control asymmetric cell divisions at the beginning of animal evolution. BioEssays 26:929–931, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The vertebrate heart comprises a variety of cell types, the majority of which are cardiomyocytes, smooth muscle and endothelial cells. Their origin is still an intriguing research topic and the question is whether these cells derive from a common or from multiple distinct progenitor cell(s). Three recent publications not only suggest the existence of a single progenitor cell that can give rise to cardiovascular lineages but additionally uncovered, at least in part, the molecular identity of such (...) a multipotent precursor cell.1-3 These findings constitute major progress in the quest for stem-cell therapies for cardiac diseases. BioEssays 29:422–426, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Recent advancements in stem-cell research have given scientists hope that new technologies will soon enable them to grow a variety of organs for transplantation into humans. Though such developments are still in their early stages, romantic prognosticators are hopeful that scientists will be capable of growing fully functioning and complex organs, such as hearts, kidneys, muscles, and livers. This raises the question of whether such profound medical developments might have other potentially fruitful applications. In the spirit of innovation, (...) this paper examines the ethical ramifications of a spin-off technology that has just begun being considered by scientists and enthusiastic entrepreneurs: animal organs grown, independently of their host animals, for food. -/- Most importantly, this paper presents the homegrown organs market as a philosopher's Gedankenexperiment come true. By comparing three of the primary arguments against the use of animals for meat production -- Peter Singer's Utilitarianism, Tom Regan's Kantianism, and Cora Diamond's non-cognitivism -- this paper proposes that the case of organs grown in a laboratory for food further accentuates the point that the critical moral difference between an animal and a slab of meat lies in the way in which the animal interacts with us, not in specific attributes or values intrinsic to that animal. It suggests that our main impetus for not eating, and even for protecting, animals ought to be grounded in our sense of who we are, in our own practical identity as ethical agents, which develops over a long course of interactive interrelations with human and non-human others. (shrink)

The Cnidaria represent the most ancient eumetazoan phylum. Members of this group possess typical animal cells and tissues such as sensory cells, nerve cells, muscle cells and epithelia. Due to their unique phylogenetic position, cnidarians have traditionally been used as a reference group in various comparative studies. We propose the colonial marine hydroid, Hydractinia, as a convenient, versatile platform for basic and applied research in developmental biology, reproduction, immunology, environmental studies and more. In addition to being a typical cnidarian (...) representative, Hydractinia offers many practical and theoretical advantages: studies that are feasible in Hydra like regeneration, pattern regulation, and cell renewal from stem cells, can be supplemented by genetic analyses and classical embryology in Hydractinia. Metamorphosis of the planula larva of Hydractinia can be used as a model for cell activation and communication and the presence of a genetically controlled allorecognition system makes it a suitable model for comparative immunology. Most importantly, Hydractinia may be manipulated at most aspects of its (short) life cycle. It has already been the subject of many studies in various disciplines, some of which are discussed in this essay. BioEssays 23:963–971, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

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.

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)

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)

This book explores the ethical and governance concerns of stem cell technology, taking a comparative approach between countries of differing socio-economic status. The book provides a typology of different stem cell types and discusses key ethical issues surrounding the use of human stem cells in research. Topics covered include the moral status of human embryos, various religious perspectives, and the challenges posed by unproven stem cell interventions. The book also examines the existing governance (...) frameworks in the UK, Singapore, and Malaysia, identifying the laws, guidelines, and advisory bodies established to address the identified ethical issues. Applicable lessons on establishing robust regulatory frameworks, fostering public trust, and ensuring responsible research practices are outlined. By providing a comparative analysis of the interplay between ethics, governance, and the socio-economic contexts of these three commonwealth countries, this book will interest health law, research ethics and bioethics scholars. (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)

A basic component of moral objections to embryonic stem cell research is the claim that human embryos have the same moral status as typical adult human beings. There is no reason to accept this claim, however, unless adult humans once existed as embryos—that is, unless the developmental history of adult humans contains embryos to which the adults are numerically identical. The purpose of this paper is to argue that there are no such identities, and hence that no adult (...) human being ever existed as an embryo. (shrink)

Stem cell research has entered the public consciousness through the media. Proponents and opponents of all such research, or of human embryonic stem cell research specifically, engage in heated exchanges in the modern public forum where stakeholders negotiate, the agora. One common claim that emerges from the fray is that a particular type of stem cell research should be pursued as the most promising path toward the reduction of suffering and untimely death for all (...) of humanity. Upon evaluation, experimental data regarding the potential role of stem cells in regenerative therapies for three conditions—spinal cord injury, type 1 diabetes, and cardiovascular disease—tell distinct, complex, and inconclusive stories. Further analyses in this article incorporate realistic considerations of a broad range of relevant factors--limited funding for biomedical research, media motives, the discordance hypothesis of evolutionary medicine, the relationship between religion and science, medical care in developing nations, and culture wars over abortion. Holistic investigation inspired by the current agora conversation supports the need to drastically change interactions regarding stem cell research so that its potential to benefit humanity may be more fully realized. (shrink)

The paper looks in detail at patients that were treated at one of the most discussed companies operating in the field of untried stem cell treatments, Beike Biotech of Shenzhen, China. Our data show that patients who had been treated at Beike Biotech view themselves as proactively pursuing treatment choices that are not available in their home countries. These patients typically come from a broad variety of countries: China, the United Kingdom, the United States, South Africa and Australia. (...) Among the patients we interviewed there seemed to be both an awareness of the general risks involved in such experimental treatments and a readiness to accept those risks weighed against the possible benefits. We interpret this evidence as possibly reflecting the emergence of risk-taking patients as ‘consumers’ of medical options as well as the drive of patients to seek treatment options in the global arena, rather than being hindered by the ethical and regulatory constraints of their home countries. Further, we found that these patients tend to operate in more or less stable networks and groups in which they interact and cooperate closely and develop opinions and assessments of available treatment options for their ailments. These patients also perform a multiple role as patients, research subjects, and research funders because they are required to pay their way into treatment and research activities. This new social dynamics of patienthood has important implications for the ethical governance of stem cell treatments. (shrink)

Stem cell research is the product of cumulative, integrated effort between and within laboratories and disciplines. The many collaborative steps that lead to that special “Eureka moment”, when something that has been a puzzle perhaps for years suddenly become clear, is among the greatest pleasures of a scientific career. In this essay, the serendipitous pathway from first acquaintance with pluripotent stem cells to advanced cardiovascular models that emerged from studying development and disease will be described. Perhaps inspiration (...) for later generations of stem cell researchers simply to follow whatever they find interesting. (shrink)

Hematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation (...) within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo‐SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies. (shrink)

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)

Discussions about the use and derivation of pluripotent human embryonic stem cells are a stumbling block in developing public policy on stem cell research. On the one hand there is a broad consensus on the benefits of these cells for science and biomedicine; on the other hand there is the controversial issue of killing human embryos. I will focus on the compromise position that accepts research on spare embryos, but not on research embryos ('discarded-created-distinction', from now on (...) d-c-d). I will point out that this viewpoint is hard to maintain. The main focus is that the 'revealed beliefs' of its defenders are inconsistent with their 'professed beliefs', more specifically with their main argument, i.e. the potentiality argument. I will point out that (1) the defenders of d-c-d actually grant a relative moral status to the human embryo, (2) this moral status is dependent on internal and external criteria of potentiality, (3) potentiality seen as a variable value that also depends on external criteria cannot justify d-c-d, and (4) an approach to human embryonic stem cell-research that would also allow the use of research embryos is more compatible with the feelings, attitudes and values of those who currently defend d-c-d and, therefore, could lead to a broader consensus and to actions that alleviate individual human suffering. (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)

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.

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)

This chapter brings a philosophical perspective to the concept of stem cell. Three general questions both clarify the concept of stem cell and emphasize its ambiguities: (1) How should we define stem cells? (2) What makes them different from non-stem cells? (3) What is their ontology? (i.e. what kind of property is “stemness”?) Following this last question, the Chapter distinguishes four conceptions of stem cells and highlights their respective consequences for the cancer (...) class='Hi'>stem cell theory. Determining what kind of property stemness is, in what context, is an urgent question, at least for therapeutic strategies against cancers. I hope that this chapter also illustrates how philosophy can be useful to biology. -/- The Chapter starts by clarifying the notions of self-renewal and differentiation. This leads to the question “can we (and if so, how) distinguish stem cells from non-stem cells through these two properties?”. From that will follow an interrogation on whether stem cells belong to a natural kind. On this issue, biologists and philosophers have framed the following alternative: either the concept of stem cell refers to entities (the cells that belong to the stem cell natural kind) or it refers to a transient and reversible cell state. I will argue that four conceptions of stemness should be distinguished rather than two. Finally, I will develop the case of the cancer stem cell (CSC) theory in order to show why it is crucial to answer the ontological question: some therapies might or might not be efficient depending on what stemness is. (shrink)

There are many kinds of clinical trials. The regulatory framework within which most drug development takes place appears to be the one that is to be applied to the development of novel stem cell-based clinical trials. In the standard drug development model, appropriate pre-clinical research is conducted, and investigators or research sponsors submit an investigational new drug application to the Food and Drug Administration.If approved, typical clinical trials start with Phase I, which is usually a trial to determine (...) the maximum tolerable dose of a drug. Phase I trials are often referred to as “safety studies” because the primary goal of Phase I research is to determine if an intervention is safe. (shrink)

Restrictions on research on therapeutic cloning are questionable as they inhibit the development of a technique which holds promise for succesful application of pluripotent stem cells in clinical treatment of severe diseases. It is argued in this article that the ethical concerns are less problematic using therapeutic cloning compared with using fertilised eggs as the source for stem cells. The moral status of an enucleated egg cell transplanted with a somatic cell nucleus is found to be (...) more clearly not equivalent to that of a human being. Based on ethical considerations alone, research into therapeutic cloning should be encouraged in order to develop therapeutic applications of stem cells. (shrink)

Stem cell-derived embryo models (SCEMs) are model embryos used in scientific research to gain a better understanding of early embryonic development. The way humans develop from a single-cell zygote to a complex multicellular organism remains poorly understood. However, research looking at embryo development is difficult because of restrictions on the use of human embryos in research. Stem cell embryo models could reduce the need for human embryos, allowing us to both understand early development and improve (...) assisted reproductive technologies. There have been several rapid advances in creating SCEMs in recent years. These advances potentially provide a new avenue to study early human development. The benefits of SCEMs are predicated on the claim that they are different from embryos and should, therefore, be exempt from existing regulations that apply to embryos (such as the 14-day rule). SCEMs are proposed as offering a model that can capture the inner workings of the embryo but lack its moral sensitivities. However, the ethical basis for making this distinction has not been clearly explained. In this current controversy, we focus on the ethical justification for treating SCEMs differently to embryos, based on considerations of moral status. (shrink)

The possibility of obtaining stem cells from human embryos has given rise to an intensive legal and ethical debate. In this paper, attention is paid to the normative disparity and ambiguity in Europe. An argument for the need for a minimal legal harmonization is made; and a prudent and flexible way to reach this successfully is suggested. Establishing a common legal framework seems to be the only way to guarantee true competitiveness for the European scientific community.

Organoids are quickly becoming an accepted model for understanding human biology and disease. Pluripotent stem cells (PSC) provide a starting point for many organs and enable modeling of the embryonic development and maturation of such organs. The foundation of PSC‐derived organoids can be found in elegant developmental studies demonstrating the remarkable ability of immature cells to undergo histogenesis even when taken out of the embryo context. PSC‐organoids are an evolution of earlier methods such as embryoid bodies, taken to a (...) new level with finer control and in some cases going beyond tissue histogenesis to organ‐like morphogenesis. But many of the discoveries that led to organoids were not necessarily planned, but rather the result of inquisitive minds with freedom to explore. Protecting such curiosity‐led research through flexible funding will be important going forward if we are to see further ground‐breaking discoveries. (shrink)

ABSTRACT One of the most important as well as most awesome achievements of modern biotechnology is the possibility of cloning human embryonic stem cells, if not human beings themselves. The possible revolutionary role of such stem cells in curative, preventive and enhancement medicine has been voiced and chorused around the globe. However, the question of the moral status of embryonic stem cells has not been clearly and unequivocally answered. Taking inspiration from the African adage that ‘the hand (...) that reaches beneath the incubating hen is not guiltless’, I attempt answering this question, from the background of traditional African moral sensibility and sensitivity. I reach the following conclusions. Stem cells in themselves do not have human status and therefore lack moral worth/value. Embryos do have human status and a morally significant line cannot be drawn between human embryos and other human beings. What is morally at stake in stem cell research is therefore the question of the source of derivation or generation of the cells, not of the cells as such. (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)

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)

Stem cells and the emerging field of regenerative medicine are at the frontiers of modern medicine. These areas of scientific inquiry suggest that in the future, damaged tissue and organs might be repaired through personalized cell therapy as easily as the body repairs itself, revolutionizing the treatment of numerous diseases. Yet the use of stem cells is fraught with ethical and public policy dilemmas that challenge scientists, clinicians, the public health community, and people of good will everywhere. (...) How shall we deal with these amazing biomedical advances, and how can we talk about potential breakthroughs with both moral and scientific intelligence? This book provides an innovative look at these vexing issues through a series of innovative Socratic dialogues that elucidate key scientific and ethical points in an approachable manner. Addressing the cultural and value issues underlying stem cell research while also educating readers about stem cells' biological function and medical applications, _Stem Cell Dialogues_ features fictional characters engaging in compelling inquiry and debate. Participants investigate the scientific, political, and socioethical dimensions of stem cell science using actual language, analysis, and arguments taken from scientific, philosophical, and popular literature. Each dialogue centers on a specific, recognizable topic, such as the policies implemented by the George W. Bush administration restricting the use of embryonic stem cells; the potential role of stem cells in personalized medicine; the ethics of cloning; and the sale of eggs and embryos. Additionally, speakers debate the use of stem cells to treat paralysis, diabetes, stroke effects, macular degeneration, and cancer. Educational, entertaining, and rigorously researched, _Stem Cell Dialogues_ should be included in any effort to help the public understand the science, ethics, and policy concerns of this promising field. (shrink)

Stem cell scientists and ethicists have focused intently on questions relevant to the developmental stage and developmental capacities of stem cells. Comparably less attention has been paid to an equally important set of questions about the nature of stem cells, their common characteristics, their non‐negligible differences and their possible developmental species specificity. Answers to these questions are essential to the project of justly inferring anything about human stem cell biology from studies in non‐human model (...) systems—and so to the possibility of eventually developing human therapies based on stem cell biology. After introducing and discussing these questions, I conclude with a brief discussion of the creation of novel model systems in stem cell biology: human‐to‐animal embryonic chimeras. Such novel model systems may help to overcome obstacles to extrapolation, but they are also scientifically and ethically contentious. BioEssays 26:1005‐1012, 2004. © 2004 Wiley Periodicals, Inc. (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 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)

Is there anything special about the ethical problems of intracerebral stem-cell transplantation and other forms of cell or tissue transplantation in the brain that provides neuroethics with a distinctive normative profile, setting it apart from other branches of medical ethics? This is examined with reference to some of the ethical problems associated with interventions in the brain such as potential changes in personal identity and potential changes in personality. It is argued that these problems are not sufficiently (...) specific to justify the autonomy of neuroethics as a separate discipline and can be handled by the established principles of medical ethics. The paper concludes with a constructive proposal how to deal with interventions in the brain for which the patient is unable to give valid ex-ante consent. (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)

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.

: In February 2004, South Korean researchers became the first in the world to successfully harvest stem cells and establish a stem cell line from a cloned human embryo. This is just one of eight possible policy options concerning human embryonic stem cell research. In practice, every kind of stem cell research can be done in one country or another. This paper evaluates the eight policy options concerning human embryonic stem cell (...) research in light of the arguments and decisions behind them. (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)

: Catholic teaching has no moral difficulties with research on stem cells derived from adult stem cells or fetal cord blood. The ethical problem comes with embryonic stem cells since their genesis involves the destruction of a human embryo. However, there seems to be significant promise of health benefits from such research. Although Catholic teaching does not permit any destruction of human embryos, the question remains whether researchers in a Catholic institution, or any researchers opposed to destruction (...) of human embryos, could participate in research on cultured embryonic stem cells, or whether a Catholic institution could use any therapy that ultimately results from such research. This position paper examines how such research could be conducted legitimately in a Catholic institution by using an ethical analysis involving a narrative context, the nature of the moral act, and the principle of material cooperation, along with references to significant ethical assessments. It also offers tentative guidelines that could be used by a Catholic institution in implementing such research. (shrink)

While some people claim that the present disagreement over embryonic stem cell research cannot be resolved, others argue that developing transparency and trust are key elements that could resolve the existing disagreements over such research. This paper reveals that transparency is not necessarily a requirement for advancing ES cell research, since in Israel, for instance, there is no transparency, and research nevertheless flourishes. Moreover, trust is not independent of cultural values and religious beliefs. Because of these beliefs, (...) the environment in Israel for ES cell research has been pragmatic and liberal. The Israeli case illustrates the key role that culture and religion can play in biomedical research; it also suggests that as far as cultural values or religious beliefs of people in Western countries strongly oppose research on embryonic tissue, it would be very difficult, if not impossible, to overcome the disagreements. (shrink)

Although the prohibition of human cloning for reproductive purposes has been proclaimed internationally, embryo stem cell research is progressively considered as a positive field for future therapeutical developments. Implicitly cloning is then becoming a tool which allows the creation of new forms of life, including human life.

In Islam, the acquisition of knowledge is a form of worship. But human achievement must be exercised in conformity with God's will. Warnings against feelings of superiority often are coupled with the command to remain within the confines of God's laws and limits. Because of the fear of arrogance and disregard of the balance created by God, any new knowledge or discovery must be applied with careful consideration to maintaining balance in the creation. Knowledge must be applied to ascertain equity (...) and justice for all of humanity. Research in Islam must be linked to the broad ethical base set forth in the Qur'an and the Sunnah. Whether embryonic stem cell research or cloning is ethically acceptable in Islam depends on the benefits derived from such applications. What is most important for the scholars is to adhere to the concepts of compassion, mercy, and benefit to everyone. (shrink)

New molecular markers for epidermal stem cells have enabled their isolation both in vitro and from the epidermis lying between hair follicles. Micro‐dissection experiments have localised a second population of stem cells within hair follicles. Epidermal stem cells have a patterned distribution in vivo. The patterning can be reconstituted in vitro, showing that it is generated by interactions between keratinocytes and that the differentiation of epidermal stem cells is regulated by signals from other keratinocytes. Recent evidence (...) from transgenic mice suggests that stem cell behaviour in the gut may be regulated by similar cell‐cell interactions in vivo. Candidate genes for mediating these interactions are the homologues of Drosophila cell fate patterning genes such as Notch and Wingless and the Cadherin family of cell‐cell adhesion molecules. The roles of stem cells and of mutations of the Patched gene in epithelial carcinogenesis are discussed. (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)