Ethics of Stem Cell Research in Medicine

Ethics of stem cell research in regeneration studies, regenerative medicine and biotechnology 1 What are the ethical aspects of stem cell research Recent findings in stem cell research and biotechnology, particularly concerning sources beyond embryonic ste...

Ethics of stem cell research in regeneration studies, regenerative medicine and biotechnology 1 What are the ethical aspects of stem cell research Recent findings in stem cell research and biotechnology, particularly concerning sources beyond embryonic stem cells, are reshaping the ethical landscape, moving towards a more nuanced understanding of "natural" stem cell therapies, a Beyond Embryonic Stem Cells: Traditional ethical concerns primarily focused on embryonic stem cells due to their potential for creating human life and the moral implications of destroying embryos for research and their applications. Emergence of Alternative Sources: Research has identified stem cells in various sources like adult tissues (bone marrow, blood), amniotic fluid, and umbilical cord blood, as well as techniques to reprogram adult cells (induced pluripotent stem cells). "Natural" Stem Cell Therapy: The concept of "natural" stem cell therapy arises from the observation that the body naturally utilizes stem cells for repair and regeneration, particularly in rapidly dividing tissues like blood cells. 2 Ethical Considerations with Alternative Sources: Somatic Stem Cells: Ethical debates surrounding the collection and use of somatic stem cells from aborted fetuses and umbilical cord blood are emerging. Induced Pluripotent Stem Cells (iPSCs): Using iPSCs, which are adult cells reprogrammed to act like embryonic stem cells, raises questions about the potential for off-target effects and the long-term safety of using altered adult cells. Perinatal Stem Cells: Stem cells found in amniotic fluid and umbilical cord blood are also being explored, but their use raises questions about consent, storage, and potential future applications. 3 An overview Biotechnology and Stem Cell Research: Biotechnology is crucial in developing tools and therapeutics by modifying and engineering stem cells. Ethical Frameworks: As stem cell research progresses, applying existing ethical frameworks and considering new ethical implications is crucial, especially regarding the clinical translation of basic stem cell knowledge into safe, effective, and accessible patient therapies. Few Examples of Stem Cell Therapies: Hematopoietic Stem Cell Transplantation: This is the only FDA- approved stem cell therapy used to treat blood cancers and other conditions. Stem Cell Therapies for Other Diseases: Research is underway to develop stem cell treatments for neurodegenerative diseases, diabetes, heart disease, and other conditions. 4 Ethical Challenges: Informed Consent: Ensuring that patients understand the risks and benefits of stem cell therapies is crucial. Access and Equity: Stem cell therapies can be costly, raising concerns about equitable access to these treatments. Scientific Rigor and Transparency: It's essential to ensure that stem cell therapies are based on sound scientific evidence and that clinical trials are conducted ethically and transparently. 5 Facts about Natural stem cell therapy The natural replacement of damaged cells by stem cells occurs actively and often in adult tissues, especially rapidly dividing cells such as blood cells. An exciting case in Boston, however, posits a kind of natural stem cell therapy provided to a mother by her fetus long after the fetus is born. Because there is a profound lack of medical intervention, this therapy seems natural enough and is unlikely to be morally suspect. Nevertheless, one may feel morally uncertain considering giving of this type of therapy to patients who would not naturally receive it. Natural stem cell therapy is a case for moral evaluation. It ultimately demonstrates the importance of permissible stem cell research and therapy, even if it is absent in an agreement about the definition of when embryonic life begins. Although one promising technology, blighted ovum utilization, uses fertilized but developmentally bankrupt eggs, it is argued that utilizing unfertilized eggs to derive totipotent stem cells obviates the moral debate over when life begins. Two existing technologies fulfill this criterion: somatic cell nuclear transfer and parthenogenic stem cell derivation. Although these technologies are far from therapeutic, concerns over the morality of embryonic stem cell derivation should not hinder their advancement. J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 6 A case study A 37 year old mother of three comes into the clinic presenting abdominal pain, marked tiredness, and puffy ankles. The standard array of diagnostic tests suggests acute liver failure. Your patient rejects all treatment options, including radical liver transplantation surgery, and decides to wait and see how her disease state progresses. Remarkably, perhaps miraculously, six months later, she shows signs of a complete recovery, despite a lack of medical intervention. Just over a year ago, researchers at the New England Medical Center in Boston presented new data on an old cell type, pregnancy-associated progenitor cells (PAPCs), which might help explain your patient's deus ex machina recovery mode. As far back as 1979, it was shown that women who give birth to sons retain some of their sons' fetal cells—for example, PAPCs, which can, in turn, give rise to multiple cell types along the hematopoietic stem cell (HSC) pathway of differentiation. J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 7 Contd… After all, the reasoning goes that the placental/blood barrier is not a perfectly selective portal, and some fetal blood and cells will cross into the maternal circulation. What is surprising, however, is the ubiquity and persistence of these fetal stem cells; they can be found in maternal circulation up to 27 years after the baby is born. These fetal stem cells were also found to localize diseased organs and repopulate them. For example, in one woman with a thyroid adenoma, a biopsy revealed two populations of cells: her germline, cancerous thyroid cells were surrounded by healthy thyroid cells derived from her son's fetus. Even more strikingly, one woman with liver disease had significant repopulation of her liver with healthy fetal-derived hepatocytes, the first indication of functional non- hematopoietic stem cell-derived PAPCs. J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 8 Contd… Whatever the mechanism involved, the idea of fetal cells expressing non‐hematopoietic markers is novel and may have important long-term health implications for the woman who has undergone pregnancy by providing her with a younger population of cells that may have different capabilities in the response to tissue injury The fertilization itself may occur not in the body but in a test tube; it is estimated that currently, in the United States, over 400,000 frozen embryos left over from in vitro fertilization treatments can be used as sources of embryonic stem cells. J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 9 Points to consider Are the fetal stem cells that save our patient's liver embryonic or adult-derived? Fetal stem cells that transfer across the placenta and remain in utero for decades have been identified as (adult) hematopoietic stem cells. Because hematopoietic stem cells cannot typically transdifferentiate into epithelial cells such as hepatocytes, the circulating stem cells in our patient are likely to be of an embryonic origin. What seems important, then, is the potential moral objection to harvesting embryos for stem cell research and therapy. It is less contentious to harvest embryos, often dozens at a time, for assisted reproduction. The sheer number of leftover embryos in thousands of fertilization clinics across the United States is a testament to the moral acceptability of the technology. J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 10  A few more ethical consideration Those who have no moral qualms against such assisted reproduction technology may nevertheless oppose using these frozen embryos to derive embryonic stem cells for research purposes. One distinction these opponents make is the seeming unnaturalness of stem cell research. They argue that the only natural way to give moral weight to the lives of frozen embryos is to implant them and carry the fetus through a full pregnancy. In vitro fertilization, it is argued, is merely assistance of reproduction, a natural phenomenon in which all healthy humans may engage. Implanting a fertilized embryo back into the mother's womb is analogous to using a respirator in assisted breathing or implanting a pacemaker to control cardiac arrhythmia. Using a fertilized embryo for scientific research disregards the natural order of things, disrespecting the sanctity of the embryo itself. J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 11 Contd… The argument for such “naturalness” is an old one: forces larger than human beings shape the external world, a higher order with which we are not to meddle. However, using naturalness as a proxy for morality fails when we consider other, highly accepted medical procedures. Very basically, perhaps, we keep a patient on life support despite his natural tendency to die. The pacemaker we install creates an artificial, not natural, rhythm in the heart. We induce childbirth, sometimes as early as 32 weeks, if we feel that the baby's health would suffer during a prolonged pregnancy. Indeed, in vitro, fertilization itself is hardly natural in that it eliminates copulation from the reproduction process. It seems that all advances in medical technology do something unnatural to alleviate pain and suffering, or to offer the joys of very natural procedures like childbearing. Intent to further natural life seems a more appropriate standard than naturalness. Moreover, regaining the ability to walk after severing a spinal cord, or seeing light again after years of retinal degeneration—potential benefits of stem cell therapy—surely weigh the same, on a scale of naturalness, as childbearing, to which these critics do not seem to object J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 12  Failure to signal the mother that development is progressing within normal limits results in spontaneous maternal reversion to a non‐pregnant state with expulsion of the failed conceptus. Such mechanisms to ensure the robustness of offspring are probably as important to species' survival as the capacity for reproduction itself. Nature celebrates success and disdains failure. An inability to develop into a healthy offspring does not, however, necessarily negate the potential of the fertilized egg to give rise to stem cells. Thus, many eggs traditionally doomed to die during embryogenesis could be utilized for stem cell production… This notion highlights the urgent need to be able to distinguish developmentally capable fertilized eggs from incapable fertilized eggs Every oak tree was once an acorn; it does not follow that acorns are oak trees or that I should treat the loss of an acorn eaten by a squirrel in my front yard as the same kind of loss as the death of an oak tree felled by a storm. Despite their developmental continuity, acorns and oak trees are different. So are human embryos and human beings J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096 13 Summary Once the technology is perfected to generate insulin‐secreting cells or spinal cord-compatible neurons from hpPS (parthenogenic stem) cells, such women could be treated with cell lines derived from their own eggs. In many ways, this type of treatment is more closely related to autologous blood transfusion than to reproductive biology. In terms of efficacy, describing a natural stem cell therapy provided to a mother by her son's fetal embryonic stem cells heralds the potent therapeutic value of a similar but heterologous stem cell therapy. In terms of morality, although there may be no consensus on when a fertilized egg becomes a life, I have argued that an egg that never becomes an embryo can, in no circumstances, constitute life. Several technologies, including those utilising parthenogenic stem cells and renucleated eggs, fall on the rectitudinous side of this moral bright line. If no life is harmed in stem cell derivation, it would be morally irresponsible to ignore the promise of stem cell therapy. Like vaccination had the power to save generations of children from crippling disease, stem cells have the power to cure many of medicine's current and future plagues. 14 J Med Ethics. 2006 Apr;32(4):235–239. doi: 10.1136/jme.2005.012096