SummarySomatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using oncogenic transcription factors. However, this method leads to genetic aberrations in iPSCs via unknown mechanisms, which may limit their clinical use. Here, we demonstrate that the supplementation of growth media with antioxidants reduces the genome instability of cells transduced with the reprogramming factors. Antioxidant supplementation did not affect transgene expression level or silencing kinetics. Importantly, iPSCs made with antioxidants had significantly fewer de novo copy number variations, but not fewer coding point mutations, than iPSCs made without antioxidants. Our results suggest that the quality and safety of human iPSCs might be enhanced by using antioxidants in the growth media during the generation and maintenance of iPSCs.

Reprogramming somatic cells to pluripotency (induced pluripotent stem cells, iPSCs) via forced expression of defined factors has become one of the most fascinating areas in biomedical research because it holds a tremendous application potential for cell therapy, disease modeling, and drug screening applications. However, cellular reprogramming is a very inefficient and metabolically demanding process commonly associated with genomic instability of the resulting iPSCs. Low reprogramming efficiency and presence of de novo genomic aberrations in iPSCs may hamper their downstream applications. Here, we review mounting studies that have tackled reprogramming efficiency and genome stability of iPSCs. In particular, we focus on the effect of oxidative stress on cellular reprogramming. We will discuss how oxidative stress influences cellular reprogramming and the mechanisms by which antioxidants promote reprogramming efficiency and preserve genome integrity of iPSCs. A reduction of oxidative stress is expected to augment reprogramming efficiency and concomitantly promote the genomic integrity of the resulting iPSCs, eventually facilitating the implementation of cellular reprogramming for downstream applications.