(i) how induced pluripotent stem cells (iPSCs) are isolated
(ii) how iPSCs can be used to study human development
(iii) how iPSCs can be used to model human disease and to develop therapies
for degenerative disease
i) iPSCs are adult stem cells that have been genetically reprogrammed to behave like the pluripotent stem cells found in embryos, i.e. can differentiate into any cell type in the human body. This was first completed successfully in mice in 2006 by Shinya Yamanaka and his team (Takahashi et al., 2006), then in humans in 2007 both by Yamanaka (Takahashi et al., 2007), and by James Thomson and his team in America independently (Yu, et al., 2007). Yamanaka and Thomson’s methods were similar. In the report by Yu et al. it is stated that “because development is dictated by epigenetic rather than genetic events, differentiation is, in principle, reversible” (Yu et al., 2007 p. 1917). In Yamanaka and team’s method, viral transduction using retroviruses containing four human transgenes (Oct3/4, Sox2, Klf4, and c-Myc) as transduction factors were used to reverse the differentiation and gene expression of human dermal fibroblasts. The resultant cells were morphologically similar to embryonic stem cells. (Takahashi et al., 2007 p. 862-863) Thomson and team used a very similar method, however used Oct4, Sox2, Nanog, and Lin28 in a lentiviral system (Yu, J, et al., 2007 p. 1917).
One of the major limitations of iPSCs currently is the presence of the viral vectors used to transduce the reprogramming factors. These have been shown in mice to cause tumors to develop due to the reactivation of c-Myc, an oncogene (a gene with the potential to transform a cell into a tumor cell in certain circumstances). iSPCs have been g...
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Park, I, Arora, N, Huo, H, Maherali, N, Ahfeldt, T, Shimamura, A, Lensch, M, Cowan, C, Hochedlinger, K, & Daley, G, 2008. Disease-Speciﬁc Induced Pluripotent Stem Cells. Cell, 134, 877-886.
Soldner, F, Hockemeyer, D, Beard, C, Gao, Q, Bell, G, Cook, E, Hargus, G, Blak, A, Cooper, O, Mitalipova, M, Isacson, O, & Jaenisch, R, 2009. Parkinson’s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors. Cell, 136, 964-977.
Saha, K, & Jaenisch, R, 2009. Technical Challenges in Using Human Induced Pluripotent Stem Cells to Model Disease. Cell Stem Cell, 5, 584-595.
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