Statement of Benefit to California:
Year 1Human induced pluripotent stem cells (hiPSCs), reprogrammed from somatic cells with defined factors, are similar to human ES cells (hESCs) and could provide ideal cell source for transplantation by avoiding immune rejection. In addition, disease-specific hiPSCs could provide improved disease models to predict drug responses in humans. The permanent genetic modification by random viral integration and spontaneous reactivation of reprogramming factors lead to cancer risk and abnormal differentiation. During the past year, we have made progresses to develop a combination of chemical and episomal approaches to reprogram human cells into iPSCs without genetic modifications. We have developed the constructs for the pre-transplant strategies to eliminate the teratomas risk of undifferentiated iPSCs. We have started to improve conditions for iPSC differentation into beta cells. In addition, we developed mouse models reconstituted with human immune system to enable us to study the immunogenicity and tolerance of cells derived from isogenic iPSCs.
Year 2During the past year, we have made significant progress in the proposed research. One most important finding is the discovery of the immunogenicity of the cells derived from induced pluripotent stem cells (iPSCs). This immunogenicity is due to the abnormal gene expression during the differentiation of iPSCs. This finding, published in the journal Nature, indicates that we need to perform more research on iPSCs before moving forward into clinical trial. Another major finding is the discovery of a safer way to improve the efficiency of iPSC production. In addition, we have made some progress in developing a genetic approach to eliminate the teratomas risk associated with the undifferentiated pluripotent stem cells.
Year 3During the past funding period, we have accomplished the established milestones. We have compared the genomic stability of iPSCs generated with various approaches. We have developed a genetic approach to eliminate the teratomas risk associated with undifferentiated pluripotent stem cells. We have evaluated the immunogenicity of cells derived from human iPSCs.
Year 4We have achieved the milestones and completed the proposed research during the no-cost extension period.