Antioxidant Regulation of Cell Reprogramming

Discovery of induced pluripotent stem cells (iPSCs) has revolutionized regeneration biology, providing further mechanistic insights and possible therapeutic applications. The original discovery by Yamanaka and co-workers showed that the expression of four transcription factors in fibroblasts resulted in the generation of iPSCs that can be differentiated into various cell types. This technology should be particularly useful for restoring cells with limited proliferative capacities such as adult heart muscle cells and neurons, in order to treat diseases affecting these cell types. More recently, iPSCs-mediated cell reprogramming has advanced to new technologies including direct reprogramming and pharmacological reprogramming. Direct reprogramming allows for the conversion of fibroblasts into cardiomyocytes, neurons or other cells by expressing multiple cell type-specific transcription factors without going through the production of iPSCs. Both iPSC-mediated reprogramming as well as direct reprogramming can also be promoted by a combination of small molecules, opening up a possibility for pharmacological therapies to induce cell reprogramming. However, all of these processes have been shown to be affected by reactive oxygen species that reduce the efficacies of reprogramming fibroblasts into iPSCs, differentiating iPSCs into target cells, as well as direct reprogramming. Accordingly, antioxidants have been shown to support these reprogramming processes and this review article summarizes these findings. It should be noted however, that the actions of antioxidants to support cell reprogramming may be through their ROS inhibiting abilities, but could also be due to mechanisms that are independent of classical antioxidant actions.