Its design caused controversy because the subjects were enrolled very soon after a serious injury, making understanding and consent challenging in this first-in-human trial and in addition making it potentially difficult to distinguish between spontaneous recovery of function and remyelination attributable to the intervention.
Patients with older lesions, though very probably in a better position to make decisions about trial participation, have scar tissue that makes remyelination unlikely or impossible.
The outcome had the potential to discourage pioneering stem cell research in the future [ 25 , 43 , 44 ]. Nonetheless, identifying the optimal time for post-injury intervention, both to maximize the potential for assessing effects on remyelination and to promote an optimal decision-making process by patient-subjects, is of ongoing concern to spinal cord injury researchers studying cell-based interventions [ 45 ]. More recently, discussions of ethical and design issues in particular stem cell trials for example, macular degeneration [ 2 ] and cardiovascular disease [ 3 ] highlight the difficult balance between the imperatives of caution and progress for first-in-human trials in high-profile areas like stem cell intervention research.
Disclosure and discussion of uncertainty with potential subjects in stem cell trials are essential in order to reduce the incidence of therapeutic misconception, whereby research subjects and also investigators and oversight bodies view research as a treatment modality or significantly overestimate the likelihood of direct benefit or both [ 19 — 22 , 41 ]. Many types of multipotent and highly multipotent stem cells have been identified as potentially suitable for clinical applications. Some of the most significant challenges faced in clinical application include how quickly to move forward in the face of great promise, great uncertainty, and great clinical need; how to regard research with investigational interventions that are difficult to standardize and impossible to undo; and how to define and describe these uncertainties in the consent process.
A growing number of prestigious academics from both science and bioethics are calling attention to these challenges [ 2 , 24 , 26 , 42 ].
Ethics of Stem Cell Research (Stanford Encyclopedia of Philosophy)
One prominent scientist commentator compares the current state of stem cell research with the histories of HSC transplantation and gene transfer research, citing several principles: risks of harm should be commensurate with the severity of the condition under study, preclinical animal models remain critically important, and gaining insight into therapeutic mechanisms is essential to the success of a line of clinical research.
Similarly, in an international survey of stem cell scientists and scholars of ethical issues in stem cell research, a prolific bioethics research group has identified increasing concerns arising from pressures for clinical translation, commercialization, and oversight of new stem cell technologies [ 14 ]. Some applications of stem cell research, such as disease modeling, drug discovery and testing, cell line banking, and commercialization of stem cell therapies, also give rise to ethical considerations specific to the field [ 11 , 12 , 14 , 16 , 24 — 26 , 28 , 29 ].
The creation and use of disease-specific iPSC lines, both alone and in combination with regenerative medicine products for example, to produce ex vivo organoids , are essential components of disease modeling and drug discovery. That promise is as yet unrealized, but questions of consent and control arise even at the bench.
Because iPSC lines are derived from the somatic cells of identifiable individuals, disclosing to those individuals the planned and envisioned uses of iPSCs derived from the cells they have donated and obtaining consent from them are critical for the creation and sharing of cell line research libraries and the future uses of biomaterials derived from previously donated biospecimens [ 24 , 26 , 47 — 50 ]. As potentially therapeutic applications proliferate for different highly multipotent stem cell types and as technical barriers to the collection and perpetuation of cell lines continue to fall, proposed research and treatment uses abound for both autologous and allogeneic stem cells.
In particular, the development of public and other broadly accessible biobanking models for stem cells derived from umbilical cord blood, amniotic fluid and placental tissue, urine, and adipose tissue holds promise for easy collection of good allograft matches for a large percentage of the population but also requires attention to ethical and policy issues [ 26 , 51 ]. Justice is a necessary but neglected consideration in all scientific research. Like many novel biotechnologies, gene- and cell-based and regenerative medicine interventions and products can be extraordinarily costly and time- and labor-intensive to develop and use.
Justice thus requires attention to the costs of developing stem cell therapies and making them available, with the goal of reducing unfair disparities in access. Cost is a standard distributive justice concern. Less commonly discussed is the effect of research funding decisions on health disparities - both priority-setting within research and priority between research funding and funding for medical care, public health, and other public goods [ 19 — 21 ].
Justice considerations are addressed in stem cell research and therapy in several ways. The first is biobanking policy and practice. The rationale for public stem cell banking is to provide a resource for transplantation of blood-forming HSCs to virtually anyone. Ideally, large-scale banking efforts could store enough different lines of broadly multipotent and pluripotent stem cells, suitable for use in regenerative medicine applications, to provide good matches for nearly the entire population of the US.
Comprehensive systems for the collection, storage, and use of stem cells of different types are, however, still in the early stages of technological and policy development. Scientific, practical, and ethical challenges include ensuring broad availability of matches for those in need, determining access for both research and therapy, refining consent forms and processes, and protecting confidentiality in labeling and information linkage [ 11 , 12 , 16 , 26 , 51 , 52 ].
Thus, large-scale biobanking of stem cell lines holds the potential to greatly increase access to stem cell therapies and reduce costs, but because available allogeneic matches may not be perfect, balancing the harms and benefits of biobanking remains critical.
Ethical and Safety Issues of Stem Cell-Based Therapy
The second justice-promoting feature of stem cell research and therapy has some similarities. Attempts to standardize and streamline production are more prevalent in stem cell-related research than elsewhere - especially in development of cell-based products and in regenerative medicine. In other new technologies like gene transfer, standardization, the development of platform technologies, and attempts at large-scale, cost-reducing production are in their infancy. This production perspective is an important step in reducing time, labor, and costs and thus increasing access, but it could also have interesting ethical implications.
Such differences could have efficacy implications that must be monitored and balanced against cost savings and access gains [ 51 ].
MSCs in IBD therapy
A final justice consideration that is heightened in the stem cell context is the simple reality that important work dedicated to improving the health of the public takes place in a market system with its attendant pressures of competition and commercialization. The attempt to ensure that hope does not become hype and that hype does not become fraud is a matter of justice.
Thus, sound practice in clinical translation, careful discussion in the media, and even seeking balance between scientific transparency and data-sharing and the intellectual property interests of industry all have important justice implications [ 13 , 16 , 24 — 29 , 42 , 53 ].
As research funding shrinks and competitive pressures grow, it may become increasingly difficult to move deliberately toward clinical translation and to allocate research resources wisely. This is especially likely as more is learned about how to reduce the risks of harm from the creation and use of iPSCs and as the costs of careful progress continue to increase. The fewer resources we have, the more important it is to allocate funds to maximize the likelihood of knowledge development in areas of greatest promise and clinical need [ 14 , 21 ].
Individual researchers may at first regard justice considerations as somewhat removed from their daily work at bench or bedside. The goals of advancing knowledge and, ultimately, improving human health are nonetheless social goals, not merely scientific goals. Researchers make vital contributions to societal views about the value of - and best directions for - scientific progress. The bill recently passed by Congress would fund stem cell research only on excess blastocysts left over from infertility treatments.
The blastocyst represents such an early stage of embryonic development that the cells it contains have not yet differentiated, or taken on the properties of particular organs or tissues—kidneys, muscles, spinal cord, and so on. This is why the stem cells that are extracted from the blastocyst hold the promise of developing, with proper coaxing in the lab, into any kind of cell the researcher wants to study or repair. The moral and political controversy arises from the fact that extracting the stem cells destroys the blastocyst.
It is important to grasp the full force of the claim that the embryo is morally equivalent to a person, a fully developed human being. This is the position of Senator Sam Brownback, Republican of Kansas, a leading advocate of the right-to-life position. SCL : What is the basis for the belief that personhood begins at conception?
MS : Some base this belief on the religious conviction that the soul enters the body at the moment of conception. Others defend it without recourse to religion, by the following line of reasoning: Human beings are not things. The reason human beings must not be treated as things is that they are inviolable. At what point do humans acquire this inviolability? The answer cannot depend on the age or developmental stage of a particular human life.
Infants are inviolable, and few people would countenance harvesting organs for transplantation even from a fetus. Every human being—each one of us—began life as an embryo. Unless we can point to a definitive moment in the passage from conception to birth that marks the emergence of the human person, we must regard embryos as possessing the same inviolability as fully developed human beings. SCL : By this line of reasoning, human embryos are inviolable and should not be used for research, even if that research might save many lives. MS : Yes, but this argument can be challenged on a number of grounds.
But this biological fact does not establish that the blastocyst is a human being, or a person. But no one would consider a skin cell a person, or deem it inviolable. Showing that a blastocyst is a human being, or a person, requires further argument. Some try to base such an argument on the fact that human beings develop from embryo to fetus to child.
Ethical Considerations on Stem Cell Research
Every person was once an embryo, the argument goes, and there is no clear, non-arbitrary line between conception and adulthood that can tell us when personhood begins. Given the lack of such a line, we should regard the blastocyst as a person, as morally equivalent to a fully developed human being.
SCL : What is the flaw in this argument? MS : Consider an analogy: although 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. Some experts believe it's wise to continue the study of all stem cell types, since we're not sure yet which one will be the most useful for cell replacement therapies.
An additional ethical consideration is that iPS cells have the potential to develop into a human embryo, in effect producing a clone of the donor. Many nations are already prepared for this, having legislation in place that bans human cloning.
MSCs in IBD therapy
Regulations and policies change frequently to keep up with the pace of research, as well as to reflect the views of different political parties. Here President Obama signs an executive order on stem cells, reversing some limits on federal research funding. White House photo by Chuck Kennedy. Governments around the globe have passed legislation to regulate stem cell research. In the United States, laws prohibit the creation of embryos for research purposes.
Scientists instead receive "leftover" embryos from fertility clinics with consent from donors. Most people agree that these guidelines are appropriate. Disagreements surface, however, when political parties debate about how to fund stem cell research. The federal government allocates billions of dollars each year to biomedical research. But should taxpayer dollars be used to fund embryo and stem cell research when some believe it to be unethical? Legislators have had the unique challenge of encouraging advances in science and medicine while preserving a respect for life. President Bush, for example, limited federal funding to a study of 70 or so hES cell lines back in While this did slow the destruction of human embryos, many believe the restrictions set back the progress of stem cell research.