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Insight Of The Decade Essay

972 words - 4 pages

Human embryonic stem cells (hESC) have for a long time stirred heated debate. Ethicists (among others) claim that life begins at conception and that the culturing of embryos for means of generating pluripotent embryonic blastomeres is as immoral as murder. Extremists also fear that the use of hESC paves the path for the laboratory procreation of humans for the sale of body parts. Another compelling argument, which holds scientific ground, is that hESC developed for other individuals may prove to be futile at the exposure to the host’s immune defense. For this reason, somatic cell nuclear transfer (SCNT) techniques were developed. SCNT works by replacing an egg genome with that of a somatic cell. While SCNT techniques allows for patient specificity, it establishes new problems dealing with the ethical nature of cloning and with the ineffectiveness in generating pluripotent cells from a mature differentiated genome (Lo et al. 2009). Recently a research team in Kyoto University, led by Shinya Yamanaka, devised a technique that removed much of the ethical dilemmas and host-specificity issues of stem cell research by reprogramming somatic cells into a less differentiated state.
Over the past decades transcription factors haves been implicated in allowing for the retention of pluripotency. The implicated factors include Oct3/4, Sox2, Nanog, Klf4 and c-Myc (Yamanaka et al. 2006). In 2006, through the use of all of these factors except Nanog, mice somatic cells were reprogrammed to become pluripotent stem cells in mice. The four factors—Oct3/4, Sox2, c-Myc, and Klf4—were inserted in the genome of mouse somatic cells via retroviral transduction. Nanog, although important in maintaining pluripotency, was not introduced retrovirally because of the interaction between c-Myc and Klf4. Klf4 indirectly increases Nanog activation by means of p53 repression. Klf4 also stimulates the anti-proliferating gene p21 which is, however, repressed by c-Myc, which is a proliferating factor (Yamanaka et al. 2006). In 2007, human fibroblasts were also reprogrammed to become pluripotent using the same four transcription factors as in mice (Yamanaka et al. 2007). Although the same four factors are conserved in mice and humans for inducing pluripotency, the downstream effects that they cause are substantially different.
These studies also revealed multiple setbacks in the study of induced pluripotent stem (iPS) cells. Of all the cells targeted, only a minute percentage of cells were actually induced to become pluripotent. In the mouse model this was thought to be the effect of a small number of multipotent cells present in the skin (0.067% of mice skin cells are multipotent). However, when inserted into bone marrow, which is enriched in multipotent stem cells, a comparably low proportion of iPS cells were generated (Yamanaka et al. 2006). It was determined that an appropriate dosage of the factors was required for pluripotency; that is, a high amount is required for the...

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