This paper examines potential ethical and legal issues arising during the research, develop- ment and clinical use of a proposed strategy in personalized medicine (PM): using human induced pluripotent stem cell (iPSC)-derived tissue cultures as predictive models of individ- ual patients to inform treatment decisions. We focus on epilepsy treatment as a likely early application of this strategy, for which early-stage stage research is underway. In relation to the research process, we examine issues associated with biological samples; (...) data; health; vulnerable populations; neural organoids; and what level of accuracy justifies using the iPSC-derived neural tissue system. In relation to clinical use, we examine potential uses in pre-natal screening, and effects on clinical decision-making. Although our focus is providing recommendations for researchers developing work in this area, we identify the novel issue of deciding on an acceptable accuracy level for the system. We also emphasize an issue thus far neglected in the ethics of PM: PM tends to represent treatment decisions as though they should be directed solely by biomedical information, but this in itself could be detri- mental to best personalizing treatment decisions in the clinic. (shrink)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron‐centric mechanisms has recently shifted towards understanding the contribution of non‐neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC‐derived microglia monocultures and co‐cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role (...) of microglia in ALS. While iPSC‐derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS‐associated mutations, microglia‐motor neuron co‐culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease‐relevant pathways in ALS and identifying potential therapeutic targets. (shrink)

The demonstration that pluripotent stem cells could be generated by somatic cell reprogramming led to wonder if these so-called induced pluripotent stem (iPS) cells would extend our investigation capabilities in the cancer research field. The first iPS cells derived from cancer cells have now revealed the benefits and potential pitfalls of this new model. iPS cells appear to be an innovative approach to decipher the steps of cell transformation as well (...) as to screen the activity and toxicity of anticancer drugs. A better understanding of the impact of reprogramming on cancer cell-specific features as well as improvements in culture conditions to integrate the role of the microenvironment in their behavior may strengthen the epistemic interest of iPS cells as model systems in oncology. (shrink)

Ford, Norman Many people think that the Catholic Church is morally opposed to all research and therapeutic use of stem cells. This is far from the truth. The Church is rightly morally opposed to all destructive use of human embryos to obtain pluripotent embryonic stem cells, but it is not opposed to pluripotent stem cells ethically derived from adult cells.

In 2006, Shinya Yamanaka and colleagues discovered how to reprogram terminally differentiated somatic cells to a pluripotent stem cell state. The resulting induced pluripotent stem cells (iPSCs) made a paradigm shift in the field, further nailing down the disproval of the long‐held dogma that differentiation is unidirectional. The prospect of using iPSCs for patient‐specific cell‐based therapies has been enticing. This promise, however, has been questioned in the last two years as several studies demonstrated (...) intrinsic epigenetic and genomic anomalies in these cells. Here, we not only review the recent critical studies addressing the genome integrity during the reprogramming process, but speculate about the underlying mechanisms that could create de novo genome damage in iPSCs. Finally, we discuss how much an elevated mutation load really matters considering the safety of future therapies with cells heavily cultured in vitro. (shrink)

Direct reprogramming of human skin cells makes available a source of pluripotent stem cells without the perceived evil of embryo destruction, but the advent of such a powerful biotechnology entangles stem cell research in other forms of moral complicity. Induced pluripotent stem cell (iPSC) research had its origins in human embryonic stem cell research and the projected biomedical applications of iPS cells almost certainly will require more embryonic stem cell (...) research. Policies that inhibit iPSC research in order to avoid moral complicity are themselves complicit in preventable harms to patients. Moral complicity may be unavoidable, but a Blue Ribbon Panel charged with assessing the need for additional embryonic stem cell lines may ease a transition from embryonic stem cell research to clinical applications of iPS cells. (shrink)

It is argued that the use of induced pluripotent stem cells for regenerative therapy may soon be ethically practicable and could sidestep the various objections pertaining to other types of stem cell (human embryonic stem cells, and stem cells obtained by altered nuclear transfer or somatic cell nuclear transfer).

The ability to convert human somatic cells into induced pluripotent stem cells (iPSCs) is allowing the production of custom‐tailored cells for drug discovery and for the study of disease phenotypes at the cellular and molecular level. IPSCs have been derived from patients suffering from a large variety of disorders with different severities. In many cases, disease related phenotypes have been observed in iPSCs or their lineage‐specific progeny. Several proof of concept studies have demonstrated that (...) these phenotypes can be reversed in vitro using approved drugs. However, several challenges must be overcome to take full advantage of this technology. Here, we highlight recent advances in the field and discuss the main challenges associated with this technology as it applies to disease modelling. (shrink)

Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and (...) that the stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy. (shrink)

No abstract available. First paragraph: In this issue’s target article, Stier and Schoene-Siefert purport to ‘depotentialize’ the argument from potentiality based on their claim that any human cell may be “converted” into a morally significant entity, and consequently, the argument from potentiality finally succumbs to a reductio ad absurdum. I aim to convey two reasons for skepticism about the innocuousness of the notion of cell convertibility, and hence, the cogency of their argument.

In lieu of an abstract, here is a brief excerpt of the content:Comments on “Moral Complicity in Induced Pluripotent Stem Cell Research”W. Malcolm Byrnes, Ph.D. and Edward J. FurtonIn his article titled “Moral Complicity in Induced Pluripotent Stem Cell Research,” Mark T. Brown (2009) unfortunately mischaracterizes my ethical analysis of the use of induced pluripotent stem (iPS) cells for replacement therapies, or treatments (Byrnes 2008). In my paper, which Brown cites, (...) I argue that, just as it is ethically acceptable for parents to allow their children and themselves to be immunized using vaccines produced by cell lines derived from human fetuses aborted in the past, it is also acceptable for persons in the future to benefit from treatments that use iPS cells validated using human embryonic stem (ES) cell lines [End Page 202] derived in the past. The assumption I make is that iPS cells would have to be shown to be functionally equivalent to human ES cells—i.e., validated—before they could be used for cell replacement treatments. (If it turns out that this assumption is incorrect, and primate or even mouse ES cells can be used for the validation, then all residual ethical problems will disappear and there will be no ethical problems whatsoever associated with iPS cells.) I wrote:... [I]n both cases, the origin of the treatment is in a one-time event: either the one-time use of aborted fetuses to obtain cell lines (e.g., MRC-5 and WI- 38) to grow weakened virus strains for vaccine production, or the one-time destruction of human embryos to validate iPS cells, which then effectively replace embryonic stem cells. In the latter case, if no additional embryonic stem cell lines are derived, then derivation of the existing lines could be considered a “one-time” event in the past, albeit an event that extended over a several-year period(Byrnes 2008, p. 287, emphasis added).Note the phrase “if no additional embryonic stem cell lines are derived.” The derivation of ES cell lines inherently involves destruction of embryos; indeed, that is why many people, including me, are opposed to human ES cell research. In my article, I am arguing that, if no additional ES cell lines are derived, then no additional human embryos will be destroyed, and the destruction of human embryos will lie in the past. In this case, embryo destruction could be considered a past event, just as the abortion of a human fetus from which vaccine-producing cell lines were derived is a past, albeit tragic, event.In the process of building his argument that proponents of iPS cell research are morally complicit in embryo destruction, Brown (2009, p. 15) casts me as being in favor of the “derivation of new embryonic stem [cell lines].” This is the exact opposite of my position. In fact, I am opposed to further destruction of human embryos. I believe that the hundreds of ES cell lines already in existence are more than sufficient to validate iPS cells and so no additional lines need to be derived. This means that no additional human embryos will need to be destroyed.Apparently based on the misperception that I support future destruction of human embryos, Brown concludes that “Byrnes’s endorsement of ongoing iPSC validation studies would seem to implicate him and those who follow his lead in formal and material complicity in what they perceive as moral evil” (p. 16). He writes that “explicit formal complicity would attach because he [Byrnes] knowingly and intentionally recommends that embryos be killed in order to facilitate a transition to a future in which no more embryos need be destroyed” (p. 16). Additionally, my “followers” and I would be guilty of “proximate material complicity” as well as “remote material complicity” (p. 16). Unfortunately, this broad condemnation is based on a misconception of my actual position.An additional problem involves Brown’s use of a quotation he attributes to me: [End Page 203]Once embryonic stem cells are used to successfully validate iPS cells, they will no longer be needed and their association with iPS cells will lie in the past. Is there not an element of sadness and resignation in accepting something (iPS cells) associated with an unjust act (destruction of an... (shrink)

According to the judgement of the European Court of Justice in 2014, human parthenogenetic stem cells are excluded from the patenting prohibition of procedures based on hESC by the European Biopatent Directive, because human parthenotes are not human embryos. This article is based on the thesis that in light of the technological advances in the field of stem cell research, the attribution of the term ‘human embryo’ to certain entities on a descriptive level as well as the (...) attribution of a normative protection status to certain entities based on the criterion of totipotency, are becoming increasingly unclear. The example of human parthenotes in particular demonstrates that totipotency is not at all a necessary condition for the attribution of the term ‘human embryo’. Furthermore, the example of hiPSC and somatic cells particularly shows that totipotency is also not a sufficient condition for the attribution of a normative protection status to certain entities. Therefore, it is not a suitable criterion for distinguishing between human embryos worthy of protection and human non-embryos not worthy of protection. Consequently, this conclusion has repercussions for the patenting question. The strict delineation between an ethically problematic commercial use of human embryos and the concomitant patenting prohibition of hESC-based procedures and an ethically unproblematic commercial use of human non-embryos and the therefore either unrestrictedly permitted or even unregulated patenting of procedures based on these alleged alternatives becomes increasingly blurred. (shrink)

Considerable hope surrounds the use of disease‐specific pluripotent stem cells to generate models of human disease allowing exploration of pathological mechanisms and search for new treatments. Disease‐specific human embryonic stem cells were the first to provide a useful source for studying certain disease states. The recent demonstration that human somatic cells, derived from readily accessible tissue such as skin or blood, can be converted to embryonic‐like induced pluripotent stem cells (hiPSCs) (...) has opened new perspectives for modelling and understanding a larger number of human pathologies. In this review, we examine the opportunities and challenges for the use of disease‐specific pluripotent stem cells in disease modelling and drug screening. Progress in these areas will substantially accelerate effective application of disease‐specific human pluripotent stem cells for drug screening. (shrink)

The phenomenal proliferation of scientific studies into the nature of induced pluripotent stem (iPS) cells following publication of the findings of Takahashi and Yamanaka little more than 2 years ago, have significantly expanded our understanding of cellular mechanisms relating to cell lineage, differentiation, and proliferation. While the full potential of iPS cell lineages for both scientific tool and therapeutic applications is as yet unclear, findings from several lines of investigation suggests that multipotential and terminally differentiated (...) class='Hi'>cells from an array of cell types are competent to undergo epigenetic reprogramming to a pluripotential state. The nature of this pluripotential state appears to be similar to, but not identical with that previously described for embryonic stem (ES) cells. Understanding the nature of this induced reprogrammed state will be critical to determining the full potential of iPS cells. Recently, this issue has been examined through an integrated analysis of the genome in fully and partially reprogrammed iPS cell lineages. These results provide a window onto the temporal components of reprogramming and suggest mechanisms by which the efficacy of reprogramming can be enhanced. (shrink)

Pluripotent stem cells have gained special attraction because of their almost unlimited proliferation and differentiation capacity in vitro. These properties substantiate the potential of pluripotent stem cells in basic research and regenerative medicine. Here three types of in vitro‐cultured pluripotent stem cells (embryonic carcinoma, embryonic stem and induced pluripotent stem cells) are compared in their historical context with respect to their different origin and properties. It became (...) evident that tumourigenicity is an inherent property of pluripotent cells based on p53 down‐regulation, expression of tumour‐related genes and high telomerase activity that allow unlimited proliferation. In addition, culture‐adapted genetic and epigenetic changes may induce tumourigenicity of pluripotent cells. The use of stem cells in regenerative medicine, however, requires non‐malignant cell types and strategies that circumvent stages of malignancy. Reprogramming strategies of adult somatic cells that avoid the tumourigenic state of pluripotency may offer alternatives for future biomedical application. (shrink)

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of (...) iPS cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes. (shrink)

The emphasis in human pluripotent stem cell (hPSC) technologies has shifted from cell therapy to in vitro disease modelling and drug screening. This review examines why this shift has occurred, and how current technological limitations might be overcome to fully realise the potential of hPSCs. Details are provided for all disease‐specific human induced pluripotent stem cell lines spanning a dozen dysfunctional organ systems. Phenotype and pharmacology have been examined in only 17 of 63 lines, primarily (...) those that model neurological and cardiac conditions. Drug screening is most advanced in hPSC‐cardiomyocytes. Responses for almost 60 agents include examples of how careful tests in hPSC‐cardiomyocytes have improved on existing in vitro assays, and how these cells have been integrated into high throughput imaging and electrophysiology industrial platforms. Such successes will provide an incentive to overcome bottlenecks in hPSC technology such as improving cell maturity and industrial scalability whilst reducing cost. (shrink)

The discovery of an alternative method of producing induced human stem cells will affect the ethical evaluation of human embryonic stem cell researchOn 20 November 2007 two groups of researchers announced that they had independently managed to produce induced Pluripotent Cells from human adult somatic cells.1 2 The two groups used slightly different procedures, but both approaches involved overexpression of a group of four genes known to be actively expressed in human embryonic (...) stem cells . The cells produced are very similar to human embryonic stem cells, they are pluripotent and they differentiate to specific cell types when treated according to protocols leading to that specific differentiation in hESC.WHAT ARE THE IMPLICATIONS OF THESE RESULTS FOR STEM CELL ETHICS?There seems to be at least two areas of debate and research where there are important implications and one area where there are none.Let us deal with the area where these results have absolutely no implications first: the contentious debate about the moral status of the embryo. Nothing in these research results will or can affect the position of those who believe that they have good arguments showing either that the embryo has no moral status at all, or that the embryo has such significant moral status that …. (shrink)

There are an increasing number of cell therapy approaches being studied and employed world‐wide. An emerging area in this field is the use of human pluripotent stem cell (hPSC) products for the treatment of injuries/diseases that cannot be effectively managed through current approaches. However, as with any cell therapy, vast numbers of functional and safe cells are required. Bioreactors provide an attractive avenue to generate clinically relevant cell numbers with decreased labour and decreased batch to batch variation. (...) Yet, current methods of performing quality control are not readily scalable to the cell densities produced during bioreactor scale‐up. One potential solution is the application of inducible/controllable suicide genes that can trigger cell death in unwanted cell types. These types of approaches have been demonstrated to increase the quality and safety of the resultant cell products. In this review, we will provide background on these approaches and how they could be used together with bioreactor technology to create effective bioprocesses for the generation of high quality and safe hPSCs for use in regenerative medicine approaches. (shrink)

Experimental therapies with embryonic stem cells and, more recently, human induced pluripotent stem cells are steadily gaining ground in clinical practice. The implementation of su...

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 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)

Recent advances in reprogramming technology do not bypass the ethical challenge of embryo sacrifice. Induced pluripotent stem cell (iPS) research has been and almost certainly will continue to be conducted within the context of embryo sacrifice. If human embryos have moral status as human beings, then participation in iPS research renders one morally complicit in their destruction; if human embryos have moral status as mere precursors of human beings, then advocacy of iPS research policy that is inhibited (...) by embryo sacrifice concerns renders one morally complicit in avoidable harms to persons. Steps may be taken to address these complicity concerns, but in the final analysis there is no alternative to achieving clarity with respect to the moral status of the human embryo. (shrink)

Glycosylation refers to the co‐ and post‐translational modification of protein and lipids by monosaccharides or oligosaccharide chains. The surface of mammalian cells is decorated by a heterogeneous and highly complex array of protein and lipid linked glycan structures that vary significantly between different cell types, raising questions about their roles in development and disease pathogenesis. This review will begin by focusing on recent findings that define roles for cell surface protein and lipid glycosylation in pluripotent stem (...) class='Hi'>cells and their functional impact during normal development. Then, we will describe how patient derived induced pluripotent stem cells are being used to model human diseases such as congenital disorders of glycosylation. Collectively, these studies indicate that cell surface glycans perform critical roles in human development and disease. (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)

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)

Recent developments in 3D cultures exploiting the self‐organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex “assembloids,” which are able to reveal cell diversities, microcircuits, and cell–cell interactions within their 3D organization. Here, the ways in which human (...) brain organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed. (shrink)

Stem cell research is very promising. The use of human embryos has been confronted with objections based on ethical and religious positions. The recent production of reprogrammed adult (induced pluripotent) cells does not – in the opinion of scientists – reduce the need to continue human embryonic stem cell research. So the debate continues.Islam always encouraged scientific research, particularly research directed toward finding cures for human disease. Based on the expectation of potential benefits, Islamic teachings (...) permit and support human embryonic stem cell research. The majority of Muslim scholars also support therapeutic cloning. This permissibility is conditional on the use of supernumerary early pre-embryos which are obtained during infertility treatment in vitro fertilization (IVF) clinics. The early pre-embryos are considered in Islamic jurisprudence as worthy of respect but do not have the full sanctity offered to the embryo after implantation in the uterus and especially after ensoulment.In this paper the Islamic positions regarding human embryonic stem cell research and therapeutic cloning are reviewed in some detail, whereas positions in other religious traditions are mentioned only briefly.The status of human embryonic stem cell research and therapeutic cloning in different countries, including the USA and especially in Muslim countries, is discussed. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. Be- cause the (...) research involves the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

Embryonic stem cells (ESCs) are now classified into two types of pluripotency: “naïve” and “primed” based upon their differing characteristics. Conventional human ESCs have much more in common with mouse epiblast stem cells and are now deemed to be primed. Naïve human ESCs that resemble mouse ESCs have recently been generated from their primed counterpart by cellular reprogramming. Isolation of naïve hESCs from human embryos has proven to be difficult. Is the inability to capture naïve hESCs (...) the result of suboptimal derivation conditions or because they are so transient they cannot be “captured” in vitro? Prevailing evidence surrounding this issue are inconclusive and require additional human embryo research. However, negative public opinion regarding human embryo research, may make this an uphill battle. The solution may come from cellular reprogramming. (shrink)

Despite decades of research, remaining safety concerns regarding disease transmission, heterotopic tissue formation, and tumorigenicity have kept stem cell‐based therapies largely outside the standard‐of‐care for musculoskeletal medicine. Recent insights into trophic and immune regulatory activities of mesenchymal stem cells (MSCs), although incomplete, have stimulated a plethora of new clinical trials for indications far beyond simply supplying progenitors to replenish or re‐build lost/damaged tissues. Cell banks are being established and cell‐based products are in active clinical trials. Moreover, significant (...) advances have also been made in the field of pluripotent stem cells, in particular the recent development of induced pluripotent stem cells. Their indefinite proliferation potential promises to overcome the limited supply of tissue‐specific cells and adult stem cells. However, substantial hurdles related to their safety must be overcome for these cells to be clinically applicable. (shrink)

Combining human embryonic stem cells with SCNT has been a gold standard of stem cell research. Adding a particular individual's genes to pluripotent stem cells might lead to the development of personalized tissue repair or replacement. Enthusiasm for human embryonic stem cell research had flagged in recent years due to controversy over the moral status of in vitro embryos, scientific misconduct by researcher Woo Suk Hwang, and the discovery that induced pluripotent (...) stem cells could be produced from somatic cells. Energy shifted to research on somatic cells, but three successes in the United States during 2013 and 2014 may reinvigorate embryonic stem cell research. (shrink)

Payment for eggs used in stem cell research puts women at unacceptable risk and encourages exploitative commodification of the female body. Thanks to the development of induced pluripotent stem cells, however, we no longer face a choice between good science and good ethics.

Disease-specific stem cell therapies, created from induced pluripotent stem cell lines containing the genetic defects responsible for a particular disease, have the potential to revolutionize the treatment of refractory chronic diseases. Given their capacity to differentiate into any human cell type, these cell lines might be reprogrammed to correct a disease-causing genetic defect in any tissue or organ, in addition to offering a more clinically realistic model for testing new drugs and studying disease mechanisms. Clinical translation (...) of these therapies provides an opportunity to design a more systematic, accessible and patient-influenced model for the delivery of medically innovative treatments to chronically ill patients. (shrink)

The recent successful conversion of adult cells into induced pluripotent stem (iPS) cells through direct reprogramming opens a new chapter in the study of disease and the development of regenerative medicine. It also provides a historic opportunity to turn away from the ethically problematic use of embryonic stem cells isolated through the destruction of human embryos. Moreover, because iPS cells are patient specific, they render therapeutic cloning unnecessary. To maximize therapeutic benefit, adult (...) stem cell research will need to be pursued in parallel with studies using iPS cells. Among the four alternative methods presented by the President’s Council on Bioethics, direct reprogram- ming is the most ethically acceptable. Nonetheless, iPS cells are tainted by their association with the human embryonic stem cell lines, derived in the past, which will be required for their validation. This concern is one that can be resolved. Human iPS cells will serve to stem the tide of human embryonic stem cell research, changing it and diverting stem cell research in a more ethical direction. (shrink)

In the US, stem cell research is at a moral impasse—many see this research as ethically mandated due to its potential for ameliorating major diseases, while others see this research as ethically impermissible because it typically involves the destruction of embryos and use of ova from women. Because their creation does not require embryos or ova, induced pluripotent stem cells offer the most promising path for addressing the main ethical objections to stem cell research; (...) however, this technology is still in development. In order for scientists to advance induced pluripotent stem cell research to a point of translational readiness, they must continue to use ova and embryos in the interim. How then are we to ethically move forward with stem cell research? We argue that there is personal integrity and value in adopting a ‘moral compromise’ as a means for moving past the moral impasse in stem cell research. In a moral compromise, each party concedes part of their desired outcome in order to engage in a process that respects the values and desires of all parties equitably. Whereas some contend that moral compromise in stem cell research necessarily involves self-contradiction or loss of personal integrity, we argue that in the US context, stem cell research satisfies many of the key pre-conditions of an effective moral compromise. To illustrate our point, we offer a model solution wherein eggs and embryos are temporarily used until non-egg and non-embryonic sources of pluripotent stem cells are developed to a state of translational readiness. (shrink)

An important contribution of Christian ethics in the pluralistic world of the twenty-first century is to emphasize inclusivity. Rather than promoting the interests of certain groups at the expense of the most vulnerable, society does well to prioritize ways forward that benefit all. For stem cell research, inclusivity entails benefiting or at least protecting the beneficiaries of treatment, the sources of materials, and the subjects of research. Adult stem cells are already benefiting many ill patients without causing (...) harm, and select adult cells may prove even more beneficial in the future. Other types of stem cells require other bodily materials such as eggs and somatic cells that should be obtained without unduly harming those who provide them. Research subjects, especially the most vulnerable, require protection as well. Should human embryos be included among them? Considerations of location, formation, individuation, and intention are here examined. Ultimately, for safety reasons as well as workability, pluripotency, and compatibility, relatively new types of pluripotent stem cells, especially induced pluripotent stem cells, warrant special priority according to an inclusive ethics. (shrink)

Stem cell researchers labor in unpredictable circumstances, beset by uncertainties allied to the study of cellular signaling behaviors. STS research, based primarily on the work of Star, has demonstrated that medical scientists often approach these vicissitudes using a type of phronesis that aims to better qualify the causes of experimental ambiguities, while also identifying optimistic reference points to help guide future research. Knowledge of this type of phronesis is extended by this article, which examines the composition of the three (...) most popular citations allied to the regenerative cellular biology/human-induced pluripotent stem cells literature. When analyzed, these papers afford evidence that the adducement of positive signals begins with sorting and categorizing. This article finds that, when representing the outcomes of this cataloging for peer-review consumption, the authors concerned predicated their observations in a perspicacious rhetoric, which serves to reinforce positive-leaning ascriptions by couching them in images of virtue, fortitude, and due diligence. The research findings presented herewith suggest that adducements of this kind may be anchored in a representational practice that could be described as “modal splicing.” This article contributes to the STS literature by observing connections between modal splicing, perspicacious representation, and knowledge affirmations in hiPSC contexts. (shrink)

This paper illuminates the explanatory role of vagueness und species membership against the background of scientific developments in recent stem cell research. With the help of the Neo-Aristotelian concept of “life form naturalism” ontologically vague entities such as stem cells, all above induced pluripotent stem cells, could be described as necessary constituents for the correct sorting and naming of natural processes and its bearers. Furthermore this specific assessment allows drawing some important ontological and (...) ethical consequences. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Future Directions for Oversight of Stem Cell Research in the United StatesCynthia B. Cohen (bio) and Mary A. Majumder (bio)Human pluripotent stem cell research, meaning research into cells that can multiply indefinitely and differentiate into almost all the cells of the body, has become a minefield in which science, ethics, and politics have collided over the last decade in the United States. President Barack (...) Obama entered this highly charged territory when he indicated during his campaign that once in office he would issue an executive order expanding federally funded human embryonic stem cell (hESC) research and introduce rigorous oversight of it (Obama 2008a & b). Candidate Obama stated that he would require that the hESC lines involved were derived with donor consent from early embryos that otherwise would be discarded following in vitro fertilization (IVF) treatment. However, in contrast with the policy of President George W. Bush, he would do so without regard to the date of their derivation. He added that he would call upon the director of the National Institutes of Health (NIH) to develop guidelines for federally funded hESC and other pluripotent stem cell research that would draw from the guidelines developed in 2005 by the National Academies of Science (NAS) for privately funded research (National Research Council 2005).A similar policy was written into the 2008 version of the Stem Cell Research Enhancement Act, which reiterates the policy enunciated in earlier versions of this bill, passed twice by the Congress but vetoed by President Bush each time (House of Representatives, 110th Congress 2008).1 Depending on how one reads the 2008 version of the act, it could also apply in certain respects to hESC research that is not federally funded. We proceed on the assumption that the act applies at least to federally funded stem cell research. Therefore, it appears that the president or the Congress, or both, will approve of an expanded policy of federal funding of hESC research, as well as other forms of human pluripotent stem cell research. [End Page 79]This policy would make the guidelines developed by a committee appointed by NAS, a prestigious private body of American scientists and related experts, the primary basis for the development of new federal guidelines for oversight of hESC research in the United States. This would have certain advantages in that those familiar with the relevant scientific issues are likely to address them accurately and stem cell investigators are apt to accept restrictions on their research written by fellow scientists and ethics and policy experts whom they perceive as strong supporters of stem cell research. However, it also would have certain disadvantages. Chief among these is that the NAS committee appointed to write guidelines for this research, in its concern to see stem cell science move forward after a period in which many scientists and others maintained that it had been unduly restricted, might have overlooked or deferred consideration of some pressing ethical and policy issues. We maintain that this is the case—although we also maintain that the NAS guidelines provide a responsible foundation for developing NIH guidelines for stem cell research. Consequently, we propose that an NIH task force charged by the director of NIH with writing new guidelines for hESC and other stem cell research should revise and expand the NAS guidelines in ways that we propose below, as well as others that it considers necessary, and make it obligatory for those seeking federal funding of such research to follow these new guidelines.We highlight certain areas in which an ethical case can be made for strengthening the existing NAS guidelines and certain areas in which more fundamental ethical reflection—and building on that, additional guideline/policy development—seems warranted. Among the sections of the NAS guidelines that need clarification and reworking, we include those regarding consent to embryo donation, which provide one of their central focuses, and the development of human-nonhuman chimeras, which they address relatively briefly. In addition, we maintain that new guidelines need to be written to address the nascent ethical and policy issues raised by the possibility that human gametes will be induced from pluripotent stem cells in the next few years and that... (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Future Directions for Oversight of Stem Cell Research in the United StatesCynthia B. Cohen (bio) and Mary A. Majumder (bio)Human pluripotent stem cell research, meaning research into cells that can multiply indefinitely and differentiate into almost all the cells of the body, has become a minefield in which science, ethics, and politics have collided over the last decade in the United States. President Barack (...) Obama entered this highly charged territory when he indicated during his campaign that once in office he would issue an executive order expanding federally funded human embryonic stem cell (hESC) research and introduce rigorous oversight of it (Obama 2008a & b). Candidate Obama stated that he would require that the hESC lines involved were derived with donor consent from early embryos that otherwise would be discarded following in vitro fertilization (IVF) treatment. However, in contrast with the policy of President George W. Bush, he would do so without regard to the date of their derivation. He added that he would call upon the director of the National Institutes of Health (NIH) to develop guidelines for federally funded hESC and other pluripotent stem cell research that would draw from the guidelines developed in 2005 by the National Academies of Science (NAS) for privately funded research (National Research Council 2005).A similar policy was written into the 2008 version of the Stem Cell Research Enhancement Act, which reiterates the policy enunciated in earlier versions of this bill, passed twice by the Congress but vetoed by President Bush each time (House of Representatives, 110th Congress 2008).1 Depending on how one reads the 2008 version of the act, it could also apply in certain respects to hESC research that is not federally funded. We proceed on the assumption that the act applies at least to federally funded stem cell research. Therefore, it appears that the president or the Congress, or both, will approve of an expanded policy of federal funding of hESC research, as well as other forms of human pluripotent stem cell research. [End Page 79]This policy would make the guidelines developed by a committee appointed by NAS, a prestigious private body of American scientists and related experts, the primary basis for the development of new federal guidelines for oversight of hESC research in the United States. This would have certain advantages in that those familiar with the relevant scientific issues are likely to address them accurately and stem cell investigators are apt to accept restrictions on their research written by fellow scientists and ethics and policy experts whom they perceive as strong supporters of stem cell research. However, it also would have certain disadvantages. Chief among these is that the NAS committee appointed to write guidelines for this research, in its concern to see stem cell science move forward after a period in which many scientists and others maintained that it had been unduly restricted, might have overlooked or deferred consideration of some pressing ethical and policy issues. We maintain that this is the case—although we also maintain that the NAS guidelines provide a responsible foundation for developing NIH guidelines for stem cell research. Consequently, we propose that an NIH task force charged by the director of NIH with writing new guidelines for hESC and other stem cell research should revise and expand the NAS guidelines in ways that we propose below, as well as others that it considers necessary, and make it obligatory for those seeking federal funding of such research to follow these new guidelines.We highlight certain areas in which an ethical case can be made for strengthening the existing NAS guidelines and certain areas in which more fundamental ethical reflection—and building on that, additional guideline/policy development—seems warranted. Among the sections of the NAS guidelines that need clarification and reworking, we include those regarding consent to embryo donation, which provide one of their central focuses, and the development of human-nonhuman chimeras, which they address relatively briefly. In addition, we maintain that new guidelines need to be written to address the nascent ethical and policy issues raised by the possibility that human gametes will be induced from pluripotent stem cells in the next few years and that... (shrink)

BackgroundThe use of human embryonic stem cells (ES cells) for the development of medical therapies is surrounded with moral concerns. The aim of this study was to assess the public’s attitudes toward the use of ES cells for treatment of Parkinson’s disease (PD) and other diseases, what factors are most important to consider when using ES cells for drug development, and if there is an association between religious beliefs and attitudes toward using ES cells (...) for medical treatment.MethodsA randomly selected sample of the Swedish public, aged 18–87-years-old, completed an online survey (n = 467). The survey assessed socio-demographics, religious views, perceived moral status of the embryo, and attitudes toward using ES cells for medical treatment of PD and other diseases. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) for positive vs. negative attitude toward using ES cells for drug development were computed using logistic regression.ResultsThe respondents were positive about using ES for treatment; specifically, 70% totally agreed that it is acceptable to use ES cells for treatment of PD, while 40% totally agreed that it is acceptable to use ES cells for treatment but induced pluripotent cells is just as efficient. Religion being of little importance in one’s life was associated with a positive attitude toward using ES cells for treatment of PD (adjusted OR 6.39, 95% CI 2.78–14.71). The importance of being able “to access new, effective treatments against diseases that do not have any treatment available” was ranked as the most important factor to consider when using ES cells for drug development.ConclusionMost respondents are positive about using ES cells for drug development, and making effective treatments accessible to those who do not have any. However, these attitudes are influenced by the specific disorder that the drug development is intended for, as well as the religious views and perceived moral status of the early embryo. (shrink)

Human pluripotent stem cells (hPSCs) have the potential to fundamentally change the way that we go about treating and understanding human disease. Despite this extraordinary potential, these cells also have an innate capability to form tumors in immunocompromised individuals when they are introduced in their pluripotent state. Although current therapeutic strategies involve transplantation of only differentiated hPSC derivatives, there is still a concern that transplanted cell populations could contain a small percentage of cells that (...) are not fully differentiated. In addition, these cells have been frequently reported to acquire genetic alterations that, in some cases, are associated with certain types of human cancers. Here, we try to separate the panic from reality and rationally evaluate the true tumorigenic potential of these cells. We also discuss a recent study examining the effect of culture conditions on the genetic integrity of hPSCs. Finally, we present a set of sensible guidelines for minimizing the tumorigenic potential of hPSC‐derived cells. © 2016 The Authors. Inside the Cell published by Wiley Periodicals, Inc. (shrink)