Application of the tumor inhibition methods in the transplant treatment of human iPS cells

Abstract

In the case of the regeneration treatment of human iPS cells (hiPSCs), the tumors may form in the transplanted tissue. It is thought that the tumors are caused by undifferentiated cells to remain in the transplanted cells and result in various problems. There are at least three methods before transplantation to overcome the tumor formation. 1. Transplanting the established cells with complete differentiation and no tumor formation, 2. Sorting and purified cells after differentiation induction, and 3. Removing unrequired cells after differentiation induction. We examined the residual undifferentiated cells in differentiation induction hiPSCs and investigated the effects of irradiation (IR), hyperthermia (HT) and drugs to the transplanted cells for preventing tumors. In differentiated induced cells treated with IR, HT and drugs, remaining undifferentiated cells were decreased. Fibroblasts and vascular endothelial cells were not affected and inhibition of cardiac muscle beating did not appear macroscopically after these treatments. Differentiated cells treated with these preventing methods were transplanted to SCID mice and the teratomatous formation was significantly decreased by IR. By flow cytometer, sorted cells after differentiation induction have some problems, which need rebuilding tissue from dissociated differentiated cells. Recently, it was reported that the hiPS lines have aberrant gene expressions and defective potential in neural differentiation, which need to be identified and eliminate before transplantation. When the high quality hiPSC lines are selected for differentiation and applied with IR, HT and drugs, residual undifferentiated cells are more eliminated. The combination with both the good hiPSCs and preventing methods would strongly inhibit post transplantation tumorigenesis.