Dopamine progenitors derived from hPSCs co-cultured with medulloblastoma

Tumorigenicity is one of the critical considerations in stem cell-based therapies. However, traditional tumorigenicity tests occasionally yield inaccurate results. Therefore, a more sensitive approach to tumorigenicity tests is needed. Here, we exposed the transplanted functional progenitors from human pluripotent stem cells (hPSCs) to the tumor microenvironment (TME) in vitro before transplantation to render them susceptible to potential abnormal proliferation or tumorigenicity. In this study, midbrain dopamine (mDA) cells derived from hPSCs were exposed to the TME through co-culturing with medulloblastoma. We found the induction of abnormal proliferation of co-cultured mDA cells both in vitro and in vivo. The mechanism of induced abnormal proliferation in co-cultured mDA cells was ascribed to the hyperactivation of proliferation-related genes, the JAK/STAT3 pathway, and cytokine stimulation. Our findings suggest that exposure of transplanted functional progenitors to the TME in vitro acts as an abnormal proliferation inducer and thereby enhances the detection ability of tumorigenicity tests.