Jamie's Final Paper

Jamie Maguire

The Potential of Adult Stem Cells

Stem cells are unspecialized cells that have the unique ability to self-renew as well as to differentiate into specialized tissue types (Blanpain et al., 2004). There are different types of stem cells, the main two being adult and embryonic. Adult stem cells (ASC) are found in almost all human tissue types, including bone marrow, skeletal muscle, nerve, placenta, and umbilical cord blood (de Wert & Mummery, 2003). Embryonic stem cells (ESC) are only found, as the name suggests, in embryos. For ESC to be collected for research, the embryo must be destroyed. This controversy can be avoided by using ASC (Doerflinger, 1999). ASC have the same medical potential as ESC while lacking the ethical dilemma, and so pose as a satisfactory alternative to embryo destroying research.
The ethical debate engulfing ESC research poses as a hurdle that only adds to the technical and practical struggles accompanied by all major forms of possible medical advancement. ESC raise deep-seated questions about life, death, and what constitutes a human being (Newton, 2007). When should a blastocyst or an embryo be considered human? If it is not yet a human being, what amount of respect should the embryo receive? Do the possible, but not certain, medical advances justify the destruction of countless human embryos? The answers to all of these questions are answered at the personal level and are widely varied. People are generally inflexible when it comes down to such fundamental pieces of their personal belief system, which makes compromises virtually impossible (Newton, 2007). Former President Ronald Reagan reiterated the American ideal of granting the ‘benefit of the doubt’ to such questions when he stated “If there’s any doubt about it, and if there’s a mystery, then shouldn’t we be extraordinarily careful?” It is a generally held notion that science should not advance at the expense of those lives it is attempting to save (Wagner, 2008). In that mindset, the possibility of destroying human life should overrule our lust for advancement.
For centuries, many biologists have been convinced that the cells which we now refer to as stem cells existed, despite the fact that they had never seen one. How else could they explain the ability to regenerate body parts held by plants and many animals; the way that the human body continually regenerates cells and tissues such as skin and blood; and the occurrence of teratomas, tumors that contain a variety of tissues and organs? The first direct evidence of stem cells was found by researchers McCulloch and Till while studying blood formation in mice in 1960. In 1964, Leroy Stevens located an abnormal sperm cell growing in a mouse embryo which eventually developed into teratoma. He termed this abnormal cell a pluripotent embryonic stem cell. British scientists Martin Evans and Matthew Kaufman were the first to isolate and culture murine ESC in vitro, a feat which they announced in 1981. The success and concurrent popularity of in vitro fertilization, beginning with Louise Brown in 1978 opened the door to begin research on human embryos. However, the success of Evans and Kaufman with mice was not achieved in humans until 1998 by independent teams led by James Thompson and John Gearheart, 20 years after the birth of the first “test-tube baby” and 17 after the first isolation and external growth of non-human ESC (Newton, 2007).
While new findings are taking ESC farther away from reaching their potential for therapeutic use in humans, the opposite is true for ASC. One major drawback previously attributed to ASC was based on the belief that ASC could only differentiate into the tissue type from which they were derived. Conventionally, the further developed the tissue, the less plasticity was assumed possible in its stem cells. Those cells present in the first three to four cell divisions of the blastocyst are coined as totipotent and have the potential to create all of the body tissues and the placenta. After these first few divisions, the stem cells are said to be pluripotent and can differentiate into any cell type except for the placenta. This is the stage that ESC are in. As more tissues become specialized, the stem cells are considered multipotent, meaning they can give rise to a limited range of cell types (Langwith, 2007). And finally it was believed that most ASC stem cells were unipotent, able only to specialize into a single cell type (Newton, 2007). Recent findings, however, have tentatively shown ASC to have flexibility close to that of ESC (Prentice, 2005). There continues to be increasing evidence pointing to much higher than anticipated plasticity of ASC as well the ability to transdifferentiate, that is, for the daughter cells to be of a different specialized tissue from an already specialized parent cell (Wulf, Jackson, Goddell, 2001).
Claims about the potential of stem cells, particularly ESC, are of monumental proportions. Aside from the increased knowledge of cellular life, treatments and cures for a wide range of diseases including multiple sclerosis, Parkinson’s disease, diabetes, and leukemia have been promised. Whether these allegations are well-founded or exaggerated has yet to be established. Inflated claims for the possibilities of stem cells would not be the first instance that the promise of scientific research was overstated (Outka, 2001).
In light of the ethical debate pertaining to ESC research, politics has stepped in. Many countries have passed legislation regarding the study of ESC. In 2001, President Bush enacted a set of criteria that must be met in order for research involving ESC to receive federal funds. Based on these parameters, funds for ESC research from the federal government could only go to stem cell lines that were (1) established before 9:00 pm Eastern Daylight Time, August 9, 2001; (2) derived from embryos originally created for reproductive purposes and were no longer needed for these purposes; and (3) informed consent must obtained, without monetary incentives, for the embryos to be donated (Stem Cell Information, 2006).
Since this policy was put into place in 2002, a major problem with existing ESC lines has been uncovered. Any therapies using the stem cell lines available for government funding (and most others) will be rejected by the human immune system. This is due to the way in which the stem cells are cultured. For the stem cells survive and proliferate outside of the body, they must be put in a solution of amino acids, glucose, and blood serum. The serum is typically from cows or pigs. The essential composition of the serum is not yet known but it has been uncovered that, among other things it contains the sialic acid known as Neu5Ac, and, in the case of serum from non-humans, Neu5Gc. These sialic acids are incorporated in the cell membrane and are involved in cell-to-cell interactions. Those cells cultured in the presence of both Neu5Ac and Neu5Gc put both of them into their cell membranes. However, the human immune system contains antibodies that recognize Neu5Gc as foreign and will reject any tissue containing this nonhuman sialic acid (Martin et al., 2005). This discovery means that very few existent ESC lines, and none among those approved by President Bush’s executive order to receive federal funds for research, can ever be used successfully in humans, adding yet another obstacle to ESC research.
For those who would argue that ASC still don’t have equal differentiation potential to ESC, scientists can now manipulate ASC into what are called induced pluripotent stem (iPS) cells. Induced pluripotent stem cells are those which look and act like ESC (Subbarao, et al., 2007). The process of reverting ASC into a pluripotent state involves the insertion of four genes in a very straight-forward process that can be performed with the tools available in any molecular biology laboratory (Holden & Vogel, 2008). In a matter of months from the first creation of iPS from murine ASC, the feat was repeated with human ASC in multiple research facilities. In the same year, iPS was successfully used in an experiment to treat sickle-cell anemia in mice (Hanna et al. 2007).
Another argument about the limitations of ASC is that they cannot reproduce indefinitely without losing differentiation potential as can ESC. This is also being proven false. The ability to reproduce indefinitely has been expressed in ASC of bone marrow (Ruiz-Canel, 2002) and umbilical cord blood (Kögler et al., 2004). It is likely only a matter of time before the same results are reproduced in other types of ASC.
It is held by some that ESC are easier to control than ASC. While they may be slightly easier to manipulate genetically, keeping them as undifferentiated stem cells is more difficult. ESC have a greater tendency to differentiate spontaneously, an action fitting to their natural purpose of developing into a full-grown human. When differentiation occurs, the value of the stem cell qua is lost. Spontaneous differentiation is less common in ASC, making them easier to control in this aspect (Ruiz-Canela, 2002).
For all of the research being done in the field, there has yet to be a single human person to benefit from ESC research. Any therapies being developed from ESC are still being tested in rodents, where they frequently result in teratomas. In contrast, ASC have been used to successfully treat over sixty-five diseases in humans (Prentice, 2005). Transplants generated from ESC or an egg cell implanted with the donor’s DNA have no decreased risk of rejection by the body’s immune system than ordinary transplants. ASC and iPS cells, however, run a drastically lower chance of being rejected, since both use the donor’s own cells, which the body will recognize as its own and not as foreign material (Outka, 2002).
While speaking before Senate, James Kelly, a paraplegic with a lot to be gained from stem cell research, very succinctly described the practicality of focusing on ASC instead of ESC research saying:
Huge obstacles stand in the way of cloned embryonic stem cells leading to cures for any condition. To overcome these obstacles, crucial funds, resources, and research careers will need to be diverted for many years to come. These obstacles include tumor formation, short and long-term genetic mutations, tissue rejection, prohibitive costs, and the need for eggs from literally tens of millions of women to treat a single major condition, such as stroke, heart disease, or diabetes. Every condition that cloned embryos someday may address is already being addressed more safely, effectively and cheaply by adult stem cells (Tada, 2003).
New research has shown that ASC have a much greater differentiation potential and the ability to be cultured without specialization than was previously anticipated, they are easier to use, are not limited by government funding opportunities to contaminated stem cell lines. They have already produced many treatments that are being used to help those suffering from a wide variety of ailments and the promise of iPS only increases their therapeutic potential. ASC have equal, if not more, potential than ESC while at the same time lacking ethical reservations, and thereby offer an adequate substitute to research that requires the destruction of human embryos.

References

Blanpain, C., Lowry, W. E., Geoghegan, A., Polak, L., & Fuchs, E., (2004). Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118(5): 635-648.

de Wert, G., & Mummery, C. (2003). Human embryonic stem cells: research, ethics and policy. Human Reproduction 18(4): 672-682.

Hanna, J., Wernig, M., Markoulaki, S., Sun, C., Meissner, A., Cassady, J., et al. (2007). Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 318(5858): 1920-1923.

Holden, C., & Vogel, G., (2008). A seismic shift for stem cell research. Science 319: 560-563.

Kögler, G., Sensken, S., Airey, A. A., Trapp, T., Müschen, M., & Feldhahn, N., et al. (2004). A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. The Journal of Experimental Medicine 200(2): 123-153.

Langwith, J (Ed.). (2007). Stem cells. Detroit, MI: Thomson Gale.

Martin, M. J., Muotri, A., Gage, F., & Varki, A., (2006). Human embryonic stem cells express an immunogentic nonhuman sialic acid. Nature Medicine 11(2): 228-232.

Newton, D. E. (2007). Stem cell research. New York, NY: Infobase Publishing.

Outka, G. (2002). The ethics of human stem cell research. Kennedy Institute of Ethics Journal 12(2): 175-213.

Prentice, D. A. (2005). Live patients & dead mice, the little-known story of the stem cells that actually work. Christianity Today 49(10).

Ruiz-Canela, M. (2002). Embryonic stem cell research: the relevance of ethics in the progress of science. Med Sci Monit, 8(5): SR21-26.

Stem Cell Information. (2006). Federal policy. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services.

Subbarao, M., Surendran, D., & Landsberg, R. (2007). Reprogramming cells. Science 318(5858): 1844-1845.

Tada, J. (2003). The threat of biotech. Christianity Today, 47(3), 60. Retrieved February 10, 2008, from Academic Search Premier database.

Wagner, V. (Ed.). (2008) Biomedical ethics. Detroit, MI: Thomson Gale.

Wulf, G. G., Jackson, K. A., Goodell, M. A., (2001). Somatic stem cell plasticity: current evidence and emerging concepts. Experimental Hematology 29(12): 1361-1370.

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