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)

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)

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)

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)

We review recent progress in the stem cell biology of the respiratory system, and discuss its scientific and translational ramifications. Several studies have defined novel stem cells in postnatal lung and airways and implicated their roles in tissue homeostasis and repair. In addition, significant advances in the generation of respiratory epithelium from pluripotent stem cells (PSCs) now provide a novel and powerful platform for understanding lung development, modeling pulmonary diseases, and implementing drug screening. Finally, breakthroughs (...) have been made in the generation of decellularized lung matrices that can serve as a scaffold for repopulation with respiratory cells derived from either postnatal or PSCs. These studies are a critical step forward towards the still distant goal of stem cell‐based regenerative medicine for diseases of lung and airways. (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.

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.

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 queries why we are more reluctant to perform stem cell research on human than on nonhuman embryos, given their remarkable similarities together with the former's greater promise for addressing human illnesses. I begin by examining two leading arguments for prohibiting stem cell research on human embryos. The first type of argument suggests that we should not interfere with the potential for human life. This argument, advanced in different ways by both utilitarians and religious believers, inadequately grapples (...) with the moral complexities raised by current technologies, such as IVF and cloning. Moreover, it fails to address the significant adverse effects of human overpopulation to both human and nonhuman well-being. The second line of argument addressed here suggests that we are morally prohibited from "playing God." This argument overlooks the various ways in which we do—indeed, we must—make life and death decisions. Further, the argument rests on an undefended assumption that we are only prohibited from making such decisions with regard to human life, while remaining free to make such decisions with regard to animals without apparent moral qualms. On the contrary, I argue that, from a fully ethical Darwinian standpoint, we must treat both human and nonhuman life with respect. Far from requiring us to abstain from difficult moral decision making, an attitude of respect toward all life requires human willingness to take responsibility for making difficult—indeed, sometimes excruciating—moral decisions. (shrink)

Pike, Gregory K The various levels at which misunderstanding exist with regards to stem cell research are discussed. The mismatch that exists between public perception and reality with regards to the same is highlighted.

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.

Gastrulation is a key milestone in the development of an organism. It is a period of cell proliferation and coordinated cellular rearrangement, that creates an outline of the body plan. Our current understanding of mammalian gastrulation has been improved by embryo culture, but there are still many open questions that are difficult to address because of the intrauterine development of the embryos and the low number of specimens. In the case of humans, there are additional difficulties associated with technical and (...) ethical challenges. Over the last few years, pluripotent stem cell models are being developed that have the potential to become useful tools to understand the mammalian gastrulation. Here we review these models with a special emphasis on gastruloids and provide a survey of the methods to produce them robustly, their uses, relationship to embryos, and their prospects as well as their limitations. (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)

The collection and storage of human tissue samples has been present in medicine for centuries, however, biobanking has recently become a dedicated activity. The technological developments that have allowed the isolation, storage and long term viability of human cells ex vivo, and to obtain relevant scientific information, including genetic information, open tremendous possibilities for advancing biomedical research. At the same time, these possibilities have raised complex ethical issues regarding tissue donors, researchers using samples and society awareness of biobanking as (...) a whole. This article aims to review the operation of stem cell biobanks, related ethical issues and the legal framework in Spain. Special consideration will be given to the new but revolutionary appearance of induced pluripotent stem cells. Most of the topics discussed here will be in the framework of banking adult derived stem cells, which do not entail in themselves any significant ethical dilemma. (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)

Stem cell research regulations are highly variable across nations, notwithstanding shared and common ethical concerns. Dominant in political debates has been the so-called embryo question. However, the permissibility of human embryonic stem cell research varies among national regulatory frameworks. Scholars have explained differences by resorting to notions of political culture, traditions of ethical reasoning, discursive strategies and political manoeuvring of involved actors. Explanations based on the role of religion or other cultural structural variables are also employed. This paper (...) analyses the emerging of the Italian regulatory framework on stem cell research using an analytical framework that considers the interplay between cultural structural features, political culture, traditions of ethical reasoning, institutional settings and the discursive and political agency of the actors involved. It aims also to explain the role of Roman Catholic Church in shaping the Italian stem cell research regulation not by treating religion as an autonomous causal factor, but through the analysis of the agency of Catholic and allied actors in the Italian political culture and institutional setting. (shrink)

Development and homeostasis of the haematopoietic system is dependent upon stem cells that have the unique ability to both self‐renew and to differentiate in all cell lineages of the blood. The crucial decision between haematopoietic stem cell (HSC) self‐renewal and differentiation must be tightly controlled. Ultimately, this choice is regulated by the integration of intrinsic signals together with extrinsic cues provided by an exclusive microenvironment, the so‐called haematopoietic niche. Although the haematopoietic system of vertebrates has been studied (...) extensively for many decades, the specification of the HSC niche and its signals involved are poorly understood. Much of our current knowledge of how niches regulate long‐term maintenance of stem cells is derived from studies on Drosophila germ cells. Now, two recently published studies by Mandal et al.1 and Krezmien et al.2 describe the Drosophila haematopoietic niche and signal transduction pathways that are involved in the maintenance of haematopoietic precursors. Both reports emphasize several features that are important for controlling stem cell behavior and show parallels to both the vertebrate haematopoietic niche as well as the Drosophila germline stem cell niches in ovary and testis. The findings of both papers shed new light on the specific interactions between haematopoietic progenitors and their microenvironment. BioEssays 29:713–716, 2007. © 2007 Wiley Periodicals, Inc. (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)

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)

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)

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)

The prelims comprise: Introduction The Mother of All Cells Embryonic Stem (ES) Cells Specialized Stem Cells Therapeutic Implications of Stem Cell Biology Cellular Philosophy and the Mind Problem The New Alchemists Stem Cell Biology: God in a Test Tube?

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)

Fast-moving and ever-changing, stem cell science and research presents ongoing ethical and legal challenges in many countries. Each development and innovation throws up new challenges. This is the case even where new developments initially seem to solve old dilemmas. Sometimes it becomes evident that new science does not in fact solve old problems and, for that reason, the ethical issues remain. In recognition of this, this book presents innovative and creative analyses of a range of ethical and legal challenges (...) raised by stem cell research and its potential and actual application. The editors of this collection have brought together experts from ethics and law to bring fresh perspectives on the use of and research on stem cells. The chapters in this collection range across a number of different issues in the debate on stem cells, from the ethical dilemmas of conducting stem cell research to those of the clinical application of stem cell technology. Each chapter gives an in-depth and comprehensive analysis of the ethical or legal issues at stake. The early chapters give engaging new expositions on the permissibility of using embryos in stem cell research, in particular challenging our views about how we view and OCyconstructOCO the embryo in debates regarding stem cells. Later chapters move on to actual and potential clinical uses of stem cells and present novel arguments about these. (shrink)

Contrary to the rarity of totipotent cells in animals, almost every cell formed by a fungus can function as a “stem cell”. The multicellular fruiting bodies of basidiomycete fungi consist of the same kind of filamentous hyphae that form the feeding phase, or mycelium, of the organism, and visible cellular differentiation is almost nonexistent. Mushroom primordia develop from masses of converging hyphae, and the stipe (or stem), cap, and gills are clearly demarcated within the embryonic fruiting body (...) long before the organ expands and unfolds through water uptake and cell wall loosening.aThough frequent references are made to gilled mushrooms in this article, the totipotent nature of fruiting body cells and lack of meristems is also applicable to basidiomycetes that spread their spore‐producing tissues inside tubes (e.g., boletes), over spines and rippled surfaces, or form spores in cavities within the fruiting body. Even in the mature mushroom, every hypha retains its totipotency. Among animals, only sponges exhibit a similar degree of developmental flexibility, which is interesting, because these simple metazoans may be relatively close relatives of fungi. BioEssays 24:949–952, 2002. © 2002 Wiley Periodicals, Inc. (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 cells are derived from the preimplantation embryo and can differentiate into virtually any other cell type, which is governed by lineage specific transcriptions factors binding to cis regulatory elements to mediate changes in gene expression. The reliance on transcriptional regulation to maintain pluripotency makes ESCs a valuable model to study the role of distal CREs such as enhancers in modulating gene expression to affect cell fate decisions. This review will highlight recent advance on transcriptional enhancers, focusing (...) on studies performed in ESCs. In addition, we argue that the Nanog locus, which encodes for an ESC-critical TF, is particularly informative because it contains multiple co-regulated genes and enhancers in close proximity to one another. The unique landscape at Nanog permits the study of ongoing questions including whether multiple enhancers function additively versus synergistically, determinants of gene specificity, and cell-to-cell variability in gene expression. Nanog encodes a transcription factor required to maintain ESC pluripotency. The Nanog locus is an ideal model to study enhancers because it contains multiple highly potent super-enhancers within a small region. Nanog and three super-enhancers are in close physical proximity but only two SEs are required for Nanog expression. (shrink)

Recent studies of prostate cancer and other tumor types have revealed significant support, as well as unexpected complexities, for the application of concepts from normal stem cell biology to cancer. In particular, the cell of origin and cancer stem cell models have been proposed to explain the heterogeneity of tumors during the initiation, propagation, and evolution of cancer. Thus, a basis of intertumor heterogeneity has emerged from studies investigating whether stem cells and/or non‐stem cells (...) can serve as cells of origin for cancer and give rise to tumor subtypes that vary in disease outcome. Furthermore, analyses of putative cancer stem cells have revealed the genetically diverse nature of cancers and expanded our understanding of intratumor heterogeneity and clonal evolution. Overall, the principles that have emerged from these stem cell studies highlight the challenges to be surmounted to develop effective treatment strategies for cancer. (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.

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)

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)

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)

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)

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)

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)

In this timely collection, some of the world's leading ethicists grapple with the variety of issues posed by human embryonic stem cell research. Investigates the moral status of the embryo including the creation of chimeras and paying for gametes (eggs and sperm) and embryos for research purposes Provides a thorough evaluation of the ethics and politics of regulating hESC research, and the privacy, confidentiality, and informed consent in the conduct of research and clinical investigations Essential reading for scientists, philosophers, (...) policy makers, and all who are interested in the ethical conduct of science Contributors include David DeGrazia, Lori Gruen, Elizabeth Harman, John Harris, Jeff McMahan, Don Marquis and Peter Singer. (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)

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)

The current model of adult neurogenesis in mammals suggests that adult‐born neurons are generated by stem cells that undergo long‐term self‐renewal, and that a lifetime supply of stem cells resides in the brain. In contrast, it has recently been demonstrated that adult‐born neurons in crayfish are generated by precursors originating in the immune system. This is particularly interesting because studies done many years ago suggest that a similar mechanism might exist in rodents and humans, with bone (...) marrow providing stem cells that can generate neurons. However, the relevance of these findings for natural mechanisms underlying adult neurogenesis in mammals is not clear, because of uncertainties at many levels. We argue here that the recent findings in crayfish send a strong signal to re‐examine existing data from rodents and humans, and to design new experiments that will directly test the contributions of the immune system to adult neurogenesis in mammals. (shrink)

Recent reports that human pluripotent stem cells can be captured in a spectrum of states with variable properties has prompted a re‐evaluation of how pluripotency is acquired and stabilised. The latest additions to the stem cell hierarchy open up opportunities for understanding human development, reprogramming, and cell state transitions more generally. Many of the new cell lines have been collectively termed ‘naïve’ human pluripotent stem cells to distinguish them from the conventional ‘primed’ cells. Here, (...) several transcriptional and epigenetic hallmarks of human pluripotent states in the recently described cell lines are reviewed and evaluated. Methods to derive and identify human naïve pluripotent stem cells are also discussed, with a focus on the uses and future developments of state‐specific reporter cell lines and cell‐surface proteins. Finally, opportunities and uncertainties in naïve stem cell biology are highlighted, and the current limitations of human naïve pluripotent stem cells considered, particularly in the context of differentiation. (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)

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)

We have developed a first generation tool for the unbiased identification and characterization of human pluripotent stem cells, termed PluriTest. This assay utilizes all the information contained on a microarray and abandons the conventional stem cell marker concept. Stem cells are defined by the ability to replenish themselves and to differentiate into more mature cell types. As differentiation potential is a property that cannot be directly proven in the stem cell state, biologists have to (...) rely on correlative measurements in stem cells associated with differentiation potential. Unfortunately, most, if not all, of those markers are only valid within narrow limits of specific experimental systems. Microarray technologies and recently next‐generation sequencing have revolutionized how cellular phenotypes can be characterized on a systems‐wide level. Here we discuss the challenges PluriTest and similar global assays need to address to fulfill their enormous potential for industrial, diagnostic and therapeutic applications. (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)

The closely related debates concerning abortion, the protection of the embryo and stem cell science have captured the legislative agenda in Mexico in recent years. This paper examines some contemporary debates related to stem cell science and the legal and political action that has followed in the wake of the latest Supreme Court judgment on abortion, which debates are directly linked to the degrees of protection of the embryo stipulated in the Mexican Constitution. While some Mexican states have (...) opted to take no further action, others, where conservative political forces are in the majority, have been very active in seeking to ensure that their constitutions are amended to protect human life from conception onwards. This intense legislative activity has not, however, been repeated at the federal level, where there is currently no overarching national regulatory framework governing stem cell research. Although major efforts have been made by the conservative block within the Senate to bring forward legislative proposals for the prohibition of human embryonic stem cell research, and despite the public expression by the federal government of its commitment to encourage inward investment and innovation in the area of biotechnology, stem cell science has, so far, remained unregulated. The legislative challenge is to resist the pressure that has been injected by religious leaders and to act in accordance with the values and principles adopted by the community in the Mexican Constitution. In the final analysis, Mexico faces particular difficulties in accommodating conservative political forces on one hand, while recognising on the other its need, as an emerging economy, to promote a progressive approach to innovation in biotechnology. (shrink)

: Successful stem cell therapies might change the natural contours of human life. If that happened, it would unsettle our ethical commitments and encourage us to see the entire natural world merely as material to be manipulated.

Inflamm‐aging is a relatively new terminology used to describe the age‐related increase in the systemic pro‐inflammatory status of humans. Here, we represent inflamm‐aging as a breakdown in the multi‐shell cytokine network, in which stem cells and stromal fibroblasts (referred to as the stem cell niche) become pro‐inflammatory cytokine over‐expressing cells due to the accumulation of DNA damage. Inflamm‐aging self‐propagates owing to the capability of pro‐inflammatory cytokines to ignite the DNA‐damage response in other cells surrounding DNA‐damaged (...) cells. Macrophages, the major cellular player in inflamm‐aging, amplify the phenomenon, by broadcasting pro‐inflammatory signals at both local and systemic levels. On the basis of this, we propose that inflamm‐aging is a major contributor to the increase in cancer incidence and progression in aged people. Breast cancer will be presented as a paradigmatic example for this relationship. (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)

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)