Alternative Methods to Obtain Stem Cells - Science Research


In 2005, the President’s Council on Bioethics convened to discuss alternative means of deriving pluripotent stem cells. Due to the nature of a blastocyst’s cellular organization, the original procedure to cultivate pluripotent stem cells lines involved the desegregation of blastomeres in developing embryos that necessitated their untimely death1. This process at its inception brought into question the ethics of using pluripotent stem cells derived from embryos, as it meant taking life to save life.

This controversy was brought to the attention of the general public and resulted in, then, President George W. Bush delivering a speech on August 9, 2001 announcing his policy decision to “allow [scientists] to explore the promise and potential of stem cell research without crossing a fundamental moral line, by providing taxpayer funding that would sanction or encourage further destruction of human embryos that have at least the potential for life.” In effect, he would allow scientific research to continue to be performed on stem cells lines that had been derived previous to that date, but would not support federally funding new stem cell lines2. Stem cell research made several minor advancements in spite of this policy, but the governmental limitations frustrated many scientists who looked to stem cells as a vast new area to be explored. Thus, the council’s main objective was to find a morally preferable way to derive healthy pluripotent cells3. Many alternatives were discussed at length, but one, I believe, has the most potential for future application.

This alternative process of deriving pluripotent stem cells is the Landry-Zucker Proposal. Donald Landry and Howard Zucker of Columbia University, in their landmark review of the situation, advocated for the derivation of pluripotent stem cell lines using blastomeres surgically removed from organismically dead embryos. Drawing upon court rulings and legislative acts, they surmised that an embryo could be technically classified as dead once the cells lost the ability of “continued and integrated cellular division, growth, and differentiation.1” The idea is that even though the embryo has lost the opportunity for further development, some healthy individual cells remain and can potentially be harvested for cultivation. In some ways, this proposal is analogous to the removal of organs from a deceased human adult3.

Modern day IVF clinics contain a vast resource of healthy pluripotent stem cells that are currently left unutilized. Dr. Laverge at the Department of Obstetrics and Gynaecology at the University Hospital in Belgium found a significant percentage of embryos preserved by cryogenic storage in IVF clinics do not continue cellular cleavage after being thawed; or lack the capacity for continued growth and development. There is a host of articles relating to scientists concerns that the reason behind the cessation of cleavage is solely chromosomal abnormalities1 3. This raises a serious issue of practicality as only healthy, diploid blastomeres can be used to derive normal functioning pluripotent stem cells. Addressing this issue, Dr. Laverge’s study found that approximately 11 percent of the non-cleaving embryos do not contain chromosomal abnormalities and would be suitable for pluripotent stem cell removal4. In a separate experiment by Dr. Alikani of the Institute for Reproductive Medicine and Science of Saint Barnabas, 107 non-viable embryos were used to extract 247 individual cells. 33% of these cells were found to differentiate and continue normal cellular activity when placed in a living host embryo5. This constitutes a major supply of healthy stem cells without the ethical issues surrounding the extraction procedure.

The Landry-Zucker proposition circumvents the ethical issues of harming human embryos during the extraction process (as they are already dead) but new ethical issues surface due to critics concerns that IVF clinics would intentionally harm embryos to increase the number available for stem cell extraction. The two Columbia professors addressed this concern by stipulating that only embryos originally created with reproductive intent, that were thought healthy enough to be kept alive in cryogenic storage, and that, after thawing, turned out to be dead could be used to derive cell cultures1. Regulatory boards could be created to ensure these guidelines were being met, and thus, no intentionally destroyed embryos would be used for research purposes.
Another practical concern resulting from this proposition is the determination of embryo death. A study analyzing the success rates of cryostorage on embryos found that 90% of recently thawed embryos that displayed no cleavage after 24 hours did not cleave any further4. This allows for an approximation system, but more exact (and less time consuming) methods are needed. The Landry-Zucker proposal suggests further studies in biochemical markers that initiate spontaneous embryo death1. If these markers were to be found, there would be a reliable way for determining embryonic death and therefore less controversy in its designation.

The reason the Landry-Zucker proposal has not been widely implemented could be a result of the significant investment of initial capital (both human resources and instrumentation) required to make the leap from current IVF policies to the ones proposed. Private companies have to weigh the pros and cons of using blastomeres derived from organismically dead embryos rather than the stem-cell lines derived before the designated deadline of August 9, 2001. Stem cells obtained from the spontaneously dead embryos must first be surgically removed, cultured, and then karyotyped to determine whether the new cell colony originated from a blastomere with genetic abnormalities (such as aneuploidy). This process obviously requires time and money that would not be needed if they were taken from the original stem cells. However, as former President Bush stated, his policy was set forth to avoid the further destruction of human embryos that have the potential for life3. As the embryos in the Landry-Zucker Proposal are from spontaneously dead embryos, the procedure cannot be said to harm them. This creates a loophole in which government funding may be acquired, offsetting the initial costs while remaining a viable way to acquire diploid blastomeres without the disruption to embryonic life.

A number of potential uses for human embryonic stem cells have been championed ever since a method for preparing them was discovered in 19986. Even if pluripotent stem cells relieve none of the numerous diseases scientists claim, research on these unspecialized cells will provide an invaluable understanding of the processes of cellular differentiation. Scientists must be given use of these cells to further our understanding of ourselves and our humble embryonic origins. This knowledge, however, should be acquired through procedures that respect the sanctity of life. I believe the Landry-Zucker Proposal is an ethically sound way to cultivate future pluripotent stem cell lines.

References:

1. Landry, D.W., Zucker, H.A. (2004). Embryonic death and the creation of human embryonic stem cells. Journal of Clinical Investigation. 114(9), 1184-1186.
(Google Scholar: Landry-Zucker Proposal, Alternative stem cells)

2. Wertz, D.C. (2002). Embryo and stem cell research in the United States: history and politics. Gene Therapy, 9, 674?678.
(Google Scholar: History of stem cells in United States, George W. Speech on stem cells)

3. The President's Council on Bioethics. (2005). White paper: alternative sources of pluripotent stem cells. Washington, DC: U.S. Government Printing Office.
(Google Scholar: Alternative sources of stem cells)

4. Laverge, H, et al. (1998). Fluorescent in-situ hybridization on human embryos showing cleavage arrest after freezing and thawing. Human Reproduction, 13, 425-429.
(Google Scholar: Freezing and thawing, cryostorage, IVF clinics, human embryos)

5. Alikani, M, Willadsen, S. (2002). Human blastocysts from aggregated mononucleated cells of two or more non-viable zygote-derived embryos. Reprod. Biomed. Online, 5, 56-58.
(Google Scholar: human embryos, non-viable, mortality rate, IVF clinics)

6. Thomson, JA, et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145-1147.
(Google Scholar: Original method for viable human stem cells, blastomeres)

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