A stem cell is any cell that exists in a relatively immature state, and is able to divide to produce one cell that replaces itself and one that will go on to become a more specialized cell type. Because stem cells replace themselves every time they divide, they are considered self-renewing, or "immortal."
There are three broad classes of stem cells: embryonic, adult, and reprogrammed. Human embryonic stem cells are obtained by the destruction of human embryos that are between three and six days old. At this early stage, cells of the embryo are still very primitive and are pluripotent; i.e., they are able to produce all of the cell types found in the mature human body.
In contrast, any stem cell that is found in a specific type of tissue (whether in an older embryo, a fetus, or a more mature individual) is considered an adult stem cell. Adult stem cells are thought to be more limited, making only the types of cells appropriate to the tissue in which they reside. Thus, they are seen as merely "multipotent."
Finally, recent studies have shown that adult body, or "somatic," cells can be reprogrammed to a state very similar to a human embryonic stem cell. These induced pluripotent stem cells, or iPSCs,1 are not identical to embryonic stem cells,2 but they are functional equivalents; i.e., when transferred to early embryos, both cell types are able to produce all of the cells of the mature body.
Stem cells offer hope for treating medical conditions that are caused by a loss of cells, either due to injury or disease. To realize this hope, several important hurdles must be overcome. First, scientists must determine how to make stem cells mature into stable tissue that survives and functions normally. Second, stem cell derivatives must be safe for transplantation. Finally, scientists must find ways of effectively using stem cells to treat or cure medical conditions.
Independent of the type of stem cell used for therapies, the pathology of many diseases is not sufficiently understood for stem cell treatments to be realistic; transplanted cells would simply fall victim to the same fatal influences that produced the disease initially. Thus, diabetes, Parkinson's disease, Alzheimer's, multiple sclerosis, and many other devastating conditions await a more thorough understanding of what causes cells to die before we can effectively treat patients with any type of stem cells.
In contrast, injuries such as those caused by heart attack or stroke present a more straightforward opportunity for stem cell therapies. In these cases, the approach to effective treatment (how to coax replacement cells into repairing damaged tissue) is likely to be similar, regardless of what kind of stem cell generates the replacement tissue. Therefore, to determine which stem cell type is likely to be the most useful, we need to ask, How do the three classes of stem cells compare in terms of the ability to produce stably differentiated cells that are safe for use in patients?
The serious safety issues raised by human embryonic stem cells have been discussed in detail.3 Embryonic stem cells produce fatal tumors indeed, such tumors are the gold-standard test for pluripotency. Embryonic stem cells can also convert to cancer cells.4 In theory, both of these problems could be addressed by maturing embryonic stem cells into more stable cell types, yet this has proved to be very difficult, with even "differentiated" cells still producing tumors.5 Despite more than a quarter century of research, the challenge of coaxing embryonic stem cells to form clinically safe cells has not been routinely overcome. Because cells derived from embryonic stem cells would be rejected by the immune system, human cloning has been proposed as a way to make patient-specific embryonic stem cells. However, cloned embryonic stem cells are known to be genetically abnormal, and this is not a simple problem to fix.6 Thus, embryonic stem cells face serious and long-standing scientific hurdles before they can be safely used in patients.
In contrast to embryonic stem cells, adult stem cells have been used in clinics for decades. Stem cells from mature tissue (i.e., present at birth or later) do not cause tumors or convert to cancer.7 Most (but not all8) adult stem cells divide more slowly than embryonic stem cells and have more restricted potency. However, some kinds of adult stem cells can differentiate into multiple cell types.9 Importantly, because adult stem cells can be obtained from the patient, or "immune matched" from birthrelated tissues like the umbilical cord and placenta, they will not be rejected.10 These combined advantages have led to significant medical advances; adult stem cells have provided benefit for over seventy medical conditions in either animal or human studies,11 and there are currently more than twenty-four hundred U.S. funded clinical trials using adult stem cells.12
Reprogrammed iPS cells have some of the advantages of adult stem cells, and some of the disadvantages of embryonic stem cells. Like embryonic stem cells, iPS cells are pluripotent and therefore produce tumors. The early techniques used to generate iPS cells carried an increased risk of tumor formation, yet the iPS technique has been significantly improved. Current approaches have eliminated any added risk, and iPSCs are now no more likely to produce tumors or cause cancer than are embryonic stem cells. Just as for embryonic stem cells, it will undoubtedly be difficult to mature iPS cells into stable, functional cell types. However, initial studies suggest that this hurdle may not be as high for iPS cells as it is for embryonic stem cells.13 Finally, iPS cells share with adult cells the advantage of being patient-specific. In the last year, scientists have produced a number of iPS cell lines from patients, to study specific diseases in the laboratory.14 Thus, iPS cells are pluripotent (making them attractive for research), yet have the significant clinical advantage of being patient-specific.
Although production of human embryonic stem cells requires the destruction of nascent human life, some claim that the potential benefit to patients justifies this research. Yet, if embryos are human beings, arguing that it is permissible to destroy someone who is small and immature in the hope of benefiting someone of larger size or greater maturity is clearly an unethical line of reasoning. The critical question is whether human embryos are mere collections of human cells or developing human beings. And this question has been thoroughly addressed by the scientific evidence:15 Embryos are developing human beings, not tumors or mere collections of human cells. They are small and immature, as all human beings once were, but they are human individuals. As Dr. Leon Kass, former chairman of the President's Council on Bioethics said, The moral issue does not disappear just because the embryos are very small or because they are no longer wanted for reproductive purposes: Because they are living human embryos, destroying them is not a morally neutral act. Just as no society can afford to be callous to the needs of suffering humanity, none can afford to be cavalier about how it treats nascent human life.16
Ethical objections to embryo-destructive research are based on religiously neutral reasoning that takes into consideration both the scientific evidence and current U.S. law regarding the protection of those who participate in experiments.17 Protecting human research subjects is an important ethical consideration. The Nazi experiments on Jews, the Tuskegee syphilis experiments on black men, and the Japanese hypothermia experiments on prisoners of war were unethical and were not justified simply because they led to new and exciting discoveries that benefited patients. Science, like all human endeavors, must operate within an ethical framework. This is not a religious objection, it is just common sense.
1 K. Takahashi and S. Yamanaka, "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors," Cell 126.4 (August 25, 2006): 663-676; and J. Yu et al., Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells," Science 318.5858 (December 21, 2007): 1917-1920. [Back]
2 Yamanaka's study indicates that 4 percent of the 32,000+ genes examined are expressed differently between iPSCs and embryonic stem cells. [Back]
3 Maureen L. Condic, "The Basics about Stem Cells," First Things 119 (January 2002): 30-34; and Maureen L. Condic, "What We Know about Embryonic Stem Cells," First Things 169 (2007): 25-29. [Back]
4 Claudia Spits et al., "Recurrent Chromosomal Abnormalities in Human Embryonic Stem Cells," Nature Biotechnology 26.12 (December 2008): 1361-1363; and Nathalie Lefort et al., "Human Embryonic Stem Cells Reveal Recurrent Genomic Instability at 20q11.21," Nature Biotechnology 26.12 (December 2008): 1364-1366. [Back]
5 See Anke Brederlau et al., "Transplantation of Human Embryonic Stem Cell-Derived Cells to a Rat Model of Parkinson's Disease: Effect of In Vitro Differentiation on Graft Survival and Teratoma Formation," Stem Cells 24.6 (2006):1433-1440. [Back]
6 David Humpherys et al., "Epigenetic Instability in ES Cells and Cloned Mice," Science 293.5527 (July 6, 2001): 95-97; Alex Bortvin et al., "Incomplete Reactivation of Oct4 Related Genes in Mouse Embryos Cloned from Somatic Nuclei," Development 130.8 (April 15, 2003): 1673-1680; David Humpherys et al., "Abnormal Gene Expression in Cloned Mice Derived from Embryonic Stem Cell and Cumulus Cell Nuclei," Proceedings of the National Academy of Sciences of the United States of America 99.20 (October 1, 2002): 12889-12894; G. Q. Tong et al., "Aberrant Profile of Gene Expression in Cloned Mouse Embryos Derived from Donor Cumulus Nuclei," Cell and Tissue Research 325.2 (2006): 231-243; Rita Vassena et al., "Deficiency in Recapitulation of Stage-Specific Embryonic Gene Transcription in Two-Cell Stage Cloned Mouse Embryos," Molecular Reproductive Development 74.12 (December 2007): 1548-1556. [Back]
7 The exception appears to be stem cells from human fetal tissue, which have produced tumors in at least four patients following transplant. See, for example, N. Amariglio et al., "Donor-Derived Brain Tumor following Neural Stem Cell Transplantation in an Ataxia Telangiectasia Patient," PLoS Medicine 6.2 (February 2009): 17. [Back]
8 Rahul Sarugaser et al., "Human Umbilical Cord Perivascular (HUCPV) Cells: A Source of Mesenchymal Progenitors," Stem Cells 23.2 (2005): 220-229; and B. M. Deasy et al., "Long-Term Self-Renewal of Postnatal Muscle-Derived Stem Cells" Molecular Biology of the Cell 16.7 (July 2005): 3323-3333. [Back]
9 Reviewed in Donald G. Phinney and Darwin J. Prockop, "Concise Review: Mesenchymal Stem/Multipotent Stromal Cells: The State of Transdifferentiation and Modes of Tissue Repair-Current Views," Stem Cells 25.11 (November 2007): 2896-2902. [Back]
10 With over four million births annually in the United States, birthassociated tissues could provide an excellent immune match to most patients. [Back]
11 List available at http://www.stemcellresearch.org/facts/treatments.htm. [Back]
12 A March 2009 search of the federal database at http://www.clinicaltrials.gov, revealed 2,461 currently funded clinical trials using adult stem cells. [Back]
13 iPS cells have been use to treat Parkinson's disease and sickle cell anemia in animal models. In an interview in Science magazine, an author of the sickle cell study indicated that efforts to conduct the study using cloning failed because cloning was too inefficient. Gretchen Vogel, "Reprogrammed Skin Cells Strut Their Stuff," ScienceNOW (December 6, 2007). For the original studies see Marius Wernig et al., "Neurons Derived from Reprogrammed Fibroblasts Functionally Integrate into the Fetal Brain and Improve Symptoms of Rats with Parkinson's Disease," Proceedings of the National Academy of Sciences of the United States of America 105.15 (April 15, 2008): 5856-5861; and Jacob Hanna et al., "Treatment of Sickle Cell Anemia Mouse Model with iPS Cells Generated from Autologous Skin," Science 318.5858 (December 1, 2007): 1920-1923. [Back]
14 F. Soldner et al., "Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors," Cell 136.5 (March 6, 2009):964-977. [Back]
15 Maureen L. Condic,"When Does Human Life Begin? A Scientific Perspective," Westchester Institute White Paper Series 1.1 (October 2008): 1-18, reprinted in National Catholic Bioethics Quarterly 9.1 (Spring 2009): 129-149. [Back]
16 Leon R. Kass, "Playing Politics with the Sick," Washington Post, October 8, 2004, http://www.washingtonpost.com/wp-dyn/articles/A16510-2004Oct7.html. [Back]
17 Protection of Human Subjects, Research Involving Pregnant Women or Fetuses, 45 CFR 46.204 (rev. June 23, 2005). [Back]