Although the products differentiated from iPSCs have not been shown to generate teratomas, it is critical to ensure the final product does not contain undifferentiated cells that have the potential to generate teratomas. Accordingly, improved protocols for differentiating human iPSCs into desired cell types with precise identity and cellular functions are needed. To this end, small molecule inhibitors that have been shown to induce selective and complete cell death of undifferentiated human pluripotent stem cells without affecting their differentiated derivatives have been identified156,157. Treatment of the iPSC-derived cellular product with these inhibitors may reduce the potential tumorigenicity. Another potential solution is to sort the iPSC-derived cells before transplantation through positive selection for desired cell types and negative selection against human ESC markers using fluorescence-activated cell sorting (FACS). Lastly, the risk of tumorigenecity can be tested in animal models prior to transplant. However, this approach may not be applicable to patients with rapid disease progression due to the long period of time associated with animal tests.
