Application

Generation of pluripotent stem cells from adult somatic cells for medical use.

Key Benefits

• No exogenous genetic manipulations, which minimize oncogenic effects, were observed in current methods.
• Peripheral blood can be used as a source of parent cell instead of fibroblasts or keratinocytes.

Market Summary

The economic and psychological tolls of chronic, degenerative, and acute diseases in the United States are enormous.Stem cell medicine has been identified as an emerging potential for the treatment of such conditions, however, obtaining embryonic tissues and isolating relatively rare cell types have limited the large-scale production of populations of pure stem cells. The development of chemically induced pluipotent stem (CiPS) cells provides a patient with a copious, immune-matched supply of pluripotent cells. In addition, ethical issues associated with the production of embryonic stem cells do not apply.

Technical Summary

Current methods used to generate iPS cells from somatic cells require overexpression of transcription factors using lentiviral vectors. Unfortunately, this approach involves both viral integration and the use of foreign genes, including known oncogenes such as c-MYC and KLF-4. Over 20% of iPS cells derived offspring developed tumors. In addition, acquiring parent cells (most commonly skin fibroblasts and keratinocytes), involves invasive surgical procedures, long-term in vitro manipulation, and may require extra procedures for decontamination. This technology describes the use of specific small molecules that can functionally replace exogenous transcription factors in producing iPS cells. Because peripheral blood is easier to attain in an aseptic manner than fibroblasts or keratinocytes, it is used as a cell source. Small molecules were identified that generated pluripotent cells and altered gene expression in CiPS cells. Embryonic stem cell marker genes were all expressed in the CiPS cells. The differentiation capacity of the CiPS cells into cell types of all three embryonic germ layers was similar to embryonic stem cells in mice.

Developmental Stage

Successfully reprogrammed mouse fibroblasts into CiPS cells using only small molecules.