Implications of genetic and epigenetic aberrations to the tumorigenicity of human pluripotent stem cells

Human pluripotent stem cells (hPSCs) hold immense promise for cell replacement therapies due to their capacity to give rise to derivatives of the three embryonic germ layers and their ability to divide indefinitely in culture. Since their first derivation less than 30 years ago, multiple hPSC-derived cell products are already in clinical trials for a range of pathologies. Nevertheless, hPSCs also possess an intrinsic tumorigenic potential and have been shown to acquire recurrent genetic and epigenetic aberrations strongly associated with cancer initiation and progression. These properties cast doubt on the safety of hPSCs and raise concerns regarding their use for transplantation. In this review, we summarize the different kinds of genetic and epigenetic abnormalities repeatedly observed in hPSCs, how they emerge, and their potential implications for the tumorigenicity of hPSC-based products. We also discuss shared and unique abnormalities found in hPSCs derived from different sources. Finally, we suggest possible methods for reducing the occurrence of these aberrations and managing their effects once they arise.