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ES Cells, Adult Stem Cells, and Biotechnology
Breaking News
Three new stories on the use of stem cells for therapeutic use have recently been published. (1) A physiological difficulty may prevent human therapeutic cloning; (2) a major ethical issue for stem cell therapy may have been circumvented, and a new one generated. (3) The mechanism by which certain adult stem cells repopulate an organ has been discovered.
The first study, from Gerald Schatten's laboratory (Simerly et al., 2003) shows that the stem cells generated by nuclear transplantation (i.e. "therapeutic cloning") may be aneuploid (have abnormal chromosome numbers) and incapable of generating human tissues. One hope for circumventing the immune rejection of stem-cell-derived tissues has been that the nucleus of the stem cell would be from the patient's own somatic cells. The product of nuclear transplantation would generate an inner cell mass from which stem cells would be derived. These stem cells would have the genetic properties of the patient who donated the nucleus. However, Simerly and colleagues found that primate oocytes sequester the microtubule-associated proteins NuMA and HSET on their meiotic spindles. When these spindles are removed, the proteins are removed with them. These proteins are essential for chromosome assembly and movement on the mitotic spindle, and without these proteins, the resulting cells become aneuploid. Therefore, unlike mice and cows, where NuMA and HSET proteins remain in the enucleated oocyte, the primate may not be able to produce viable stem cells from the current technological procedures.
The second study, from Hans Sch?ler's laboratory (Hbner et al., 2003) circumvents one of the major ethical obstacles to therapeutic cloning. If therapeutic cloning becomes a viable form of therapy, then a major question becomes: who is providing all those human oocytes? Many people were concerned that women in poorer nations would be pressured into selling their oocytes to commercial firms that would supply the demand in the wealthier countries. Hbner and her colleagues demonstrated that mouse embryonic stem cells routinely form oocytes in culture. Moreover, these oocytes organized the cells around them to become follicle cells, enabling the oocytes to mature and undergo meiosis. If stem cells could make meiotically mature oocytes, then this would become the source of the human oocytes needed for stem cell therapy. However,this study also raises another ethical issue. One of the arguments used to counter the notion that stem cells could, themselves, become embryos and infants is that these cells are not totipotent. That is to say, these cells could make the derivatives of the inner cell mass, but not the trophoblast. Thus, they could not become embryos. However, if the cells could become oocytes, and if (as has been seen) these oocytes can undergo normal development, then some embryonic stem cells can revert back totipotency.
The third study concerns adult stem cells. Hematopoietic stem cells seem to have the ability to develop not only into blood cells, but also into liver cells. Recent studies by Wang and colleagues (2003) and by Vassilopoulos and colleagues (2003) indicate (1) that stem cells from adult mouse bone marrow can repair liver damage in mice, and (2) they accomplish this by fusing with the existing mouse liver cells, thereby changing their developmental fate. Instead of a blood stem cell entering the area of the liver and differentiating according to its new location, it appears that the stem cells fuse with liver cells, and this fusion gives them the ability to produce liver-specific tissue. Moreover, their stem cell qualities enable them to continue dividing. These papers used mice that had a genetic defect for the production of the fumarylacetoacetate transferase enzyme (Fah). This is a liver-specific enzyme and not found in blood stem cells. The purified blood stem cells colonized the liver and became liver tissue, and produced this missing enzyme (from the wild-type genes of the blood stem cell). Moreover, the new liver tissue had genetic markers of the host (liver) and the donor (blood stem cells) strains, indicating that the tissue was produced by cell fusions. Thus, adult stem cells may indeed be able to generate new tissue and heal genetic disease, but not by the transdetermination mechanism originally believed to be the case.
References
Hübner, K. and nine others. 2003. Derivation of oocytes from mouse embryonic stem cells. Sciencexpress. www.sciencexpress.org (1 May 2003).
Simerly, C. and 11 others. 2003. Molecular correlates of primate nuclear transfer failures. Science 300: 297.
Vassilopoulos, G., Wang, P.-R., and D. W. Russell. 2003. Transplanted bone marrow regenerates liver by cell fusion. Nature 422: 901–904.
Wang, X. and nine others. 2003. Cell fusion is the principal source of bone-marrow-derived heptocytes. Nature 422: 897n901.
Ethical and Public Policy Issues in Stem Cell Research
Ethical and Public Policy Issues Concerning Stem Cell Research
Other Websites Updating Ethical and Public Policy Considerations of Stem Cell Therapies and Research
NIH Stem Cell Site This site contains the NIH human embryonic stem cell registry of embryonic stem cell lines for which federal funding is permitted; it also contains implementation issues for stem cell research, congressional testimony concerning stem cell studies, and federal guidelines for stem cell research.
British position on human embryonic stem cells.
The National Academy of Scienceis report: Stem Cells and the Future of Regenerative Medicine, recommending public funding for stem cell research. (Summary.)
The Presidentis Council on Bioethics Report: Human Cloning and Human Dignity. (Background testimony for this report.)
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