Efficient derivation of human induced pluripotent stem cells with a c-Myc-free non-integrating episomal vector
Human induced pluripotent stem cells (hiPSCs) can self-renew indefinitely and have the potential to differentiate into all cell types in the human body, thus hold great promise in regenerative medicine, drug screening and developmental biology studies. However, integrating retroviral (Takahashi et al., 2007) or lentiviral (Hockemeyer et al., 2008) gene delivery systems and the exogenous oncogene c-Myc ( Takahashi et al., 2007 and Hockemeyer et al., 2008) have been typically used in the reprogramming process, which could increase risks of insertional mutations or epigenetic abnormalities and consequently pose biosecurity concerns for basic research and clinical applications of hiPSCs. To circumvent the problems mentioned above, non-integrating reprogramming methods (Schlaeger et al., 2015) with fewer or no factors (Hou et al., 2013) have been developed, albeit at low reprogramming efficiency. Therefore, we sought to develop a highly efficient method to reprogram human somatic cells into hiPSCs by a non-integrating gene delivery system in the absence of oncogenes.