Technical approaches to induce selective cell death of pluripotent stem cells

Abstract

Despite the recent promising results of clinical trials using human pluripotent stem cell (hPSC)-based cell therapies for age-related macular degeneration (AMD), the risk of teratoma formation resulting from residual undifferentiated hPSCs remains a serious and critical hurdle for broader clinical implementation. To mitigate the tumorigenic risk of hPSC-based cell therapy, a variety of approaches have been examined to ablate the undifferentiated hPSCs based on the unique molecular properties of hPSCs. In the present review, we offer a brief overview of recent attempts at selective elimination of undifferentiated hPSCs to decrease the risk of teratoma formation in hPSC-based cell therapy.

Keywords: Apoptosis; Human pluripotent stem cells; Safe stem cell therapy; Selective cell death; Teratoma.

Fig. 1

An example of the procedure of human pluripotent stem cell-based cell therapy for assuring teratoma-free cell therapy. After differentiation to the desirable cell type, an assay should be performed to check for possible contamination of tumorigenic hPSCs, even after enriching the desirable cell types. Likewise, even after additional steps have been taken for ablating residual tumorigenic hPSCs, cell therapy should only be conducted after a highly sensitive assay has been performed that validates that no tumorigenic hPSCs remain in order to guarantee teratoma-free cell therapy