Reprogramming and Somatic Cell Nuclear Transfer (SCNT)

Embryonic stem cells (ESCs) can proliferate indefinitely, maintain an undifferentiated pluripotent state and differentiate into any cell type. The ability of ESCs to differentiate into any cell type means we may be able to utilize these cells to cure or alleviate the symptoms of many degenerative diseases. However, allogenic human ESCs (ESCs derived from spare IVF embryos) are genetically divergent from the host/patient, this means that transplantation of allogenic ESC-derived cell-types into a patient (without immunosuppressive drugs) will incite an immune response and result in the rejection of the transplanted ESCs. A solution to the immune rejection problem would be to generate isogenic ESCs from somatic cell nuclear transfer (SCNT) embryos derived from the patients' own cells, a concept commonly referred to as "therapeutic cloning". However, the feasibility of human therapeutic cloning is severely limited by the low blastocyst production efficiency observed following human SCNT. Our current goals are to investigate if the therapeutic cloning protocols we have successfully used in the non-human primate will work with human oocytes, to understand the underlying mechanisms of SCNT-based reprogramming and to develop basic research and clinical applications based on the SCNT-reprogrammed cell lines.

Recently, several independent research groups have derived induced pluripotent stem (iPS) cells from human skin fibroblasts by transducing the cells with either OCT4, SOX2, CMYC and KLF4 or OCT4, SOX2, NANOG and LIN28. These iPS cells have many similar characteristics to embryonic stem cells and thus yield great potential in future stem cell research. However, more research is needed to determine if these iPS cells are capable of giving rise to all the major cell lineages in the body and finally treating patients.

We are exploring different approaches to harvest the potentials of human embryonic stem cells as well as alternative pluripotent cells such as iPS cells to treat diseases.

Articles related to this topic:

Takahashi et al., 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131(5), 861-72. Abstract »

Yu et al., 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science. 318, 1917-20. Abstract »

Byrne et al., 2007. Producing primate embryonic stem cells by somatic cell nuclear transfer. Nature. 450, 497-502. Abstract »

Wernig, M., et al., 2007. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature. 448, 318-24. Abstract »

Wilmut, I., et al., 1997. Viable offspring derived from fetal and adult mammalian cells. Nature. 385, 810-3. Abstract »

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