ASSAY FOR MUTATIONS IN STEM CELLS AND THEIR DERIVATIVES

DESCRIPTION (provided by applicant): Stem cell-based therapies hold great promise for the treatment of numerous debilitating diseases and conditions. However, the success of this approach is dependent upon maintenance of genetic integrity in these cells, b oth before and after induction of differentiation to yield specific, functional cell types in vitro, and/or transplantation of differentiated derivatives to mitigate defects in patients in vivo. Currently, the primary method available to assess the genetic integrity of stem cells or their derivatives is karyotyping. This method detects abnormalities in chromosome number or gross defects in chromosomal structure, but does not detect point mutations, including base substitutions, small deletions or small inse rtions, that are responsible for a significant proportion of genetic aberrations leading to abnormal cellular function, including tumorigenesis. This proposal will support the development and validation of a transgene-based assay to determine the frequency and spectrum of point mutations in human and nonhuman primate stem cells and their derivatives. This assay will facilitate a highly relevant assessment of genetic integrity that will provide a critically needed level of quality control and safety assuranc e during the development of a variety of different stem cell-based therapeutic approaches. As the work evolves into Phase II, multiple potential products and tools will be derived from unique non-human primate rhesus and baboon cells and from new and exist ing human cell lines.