STUDENT 3
The Potential of Adult Stem Cells
Stem cells are unspecialized cells that can self-renew as well as differentiate into specialized tissue types(Blanpain et al. 2004) . Stem cells from embryos (ESC) have been heralded as the key to curing numerous devastating illnesses. In fact, ESC have received so much public attention that they are what first comes to mind when most people think about stem cells. But the destruction of human embryos entailed by research of embryonic stem cells has created a moral impasse regarding the humanity and intrinsic rights of an embryo. Adult stem cells (ASC), which are found in almost all tissue types, including bone marrow, skeletal muscle, nerve, placenta, and umbilical cord blood (de Wert & Mummery, 2003), haven’t received as much attention as ESC. The controversy caused by the destruction of embryos for ESC research can be avoided by using ASC instead (Doerflinger, 1999). ASC have the same medical potential as ESC while lacking the ethical dilemma, and so pose as a superior 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 uncertain, medical advances justify the destruction of countless human embryos? The answers to all of these questions are answered differently by individual people and are widely varied. People are generally inflexible when it comes down to such fundamental pieces of their personal belief system, which makes compromises on this issue 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). Bearing these two things in mind, the mere possibility of destroying human life should overrule our desire 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 formation of a human with multiple tissue types from a single cell? How else could they make sense of 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 (Stevens, 1970). 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 (Evans & Kaufman, 1981). The success and concurrent popularity of in vitro fertilization, beginning with the birth of Louise Brown in 1978, opened the door to begin research on human embryos. However, due to the high level of technical skills required and the ethical implications, the success of Evans and Kaufman with mice was not achieved in humans until 1998. The success was released 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). Finally, human ESC could be studied and their plasticity tested.
Conventionally, the further developed the tissue, the less plasticity was assumed possible in its stem cells. Accordingly, those cells present in the first three to four cell divisions of the embryo are referred to 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. 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 unipotent cells, which are able to specialize into only a single cell type (Newton, 2007). In this arrangement, ESC are considered pluripotent, while ASC are only unipotent or, possibly, multipotent.
Due to their plasticity, claims about the potential of stem cells, particularly ESC, are of monumental proportions. Aside from the increased knowledge of cell biology and development, 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).
The ethical complications pertaining to ESC research has given rise to a political debate about it. 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) for which informed consent was 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 these sialic acids 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.
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, that they were only multipotent at best. 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).
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, Srendran, & Landsberg, 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-Canela, 2002) and umbilical cord blood (Kögler et al., 2004). It is likely to be 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 ESC 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 stem cell 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. Since the cells in the transplant will not have the identifying markers of the patient, the immune system will recognize them as foreign. 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 and thus a possible beneficiary of 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…. 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, and 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. Added to that, no embryos need to be killed to study ASC. All of these things give ASC equal, if not more, potential than ESC while at the same time lacking ethical reservations, and thereby offer a more than adequate substitute to research that requires the destruction of human embryos. There is nothing to justify taking even the slightest risk of destroying human life when there exists such a superior option.
References
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