Effects of antioxidants on the quality and genomic stability of induced pluripotent stem cells

Abstract

Effects of antioxidants on the quality and genomic stability of induced pluripotent stem (iPS) cells were investigated with two human iPS cell lines (201B7 and 253G1). Cells used in this study were expanded from a single colony of each cell line with the addition of proprietary antioxidant supplement or homemade antioxidant cocktail in medium, and maintained in parallel for 2 months. The cells grew well in all culture conditions and kept “stemness”. Although antioxidants modestly decreased the levels of intracellular reactive oxygen species, there were no differences in the expression of 53BP1 and pATM, two critical molecules related with DNA damage and repair, under various culture conditions. CGH analysis showed that the events of genetic aberrations were decreased only in the 253G1 iPS cells with the addition of homemade antioxidant cocktail. Long-term culture will be necessary to confirm whether low dose antioxidants improve the quality and genomic stability of iPS cells.

Effects of Antioxidant Supplements on the Survival and Differentiation of Stem Cells

“…Recently, it has been found that high-dose antioxidants downregulates DNA repair-related kinases, which conversely results in genomic instability of iPSCs [21]. Therefore, adjusting the dose of supplementary antioxidants is critical.…”

Inducing pluripotency in vitro: recent advances and highlights in induced pluripotent stem cells generation and pluripotency reprogramming

“…Some of the recent studies have sought to address nutritional requirements for pluripotency reprogramming and determined that some common dietary supplements have noteworthy potential for improving reprogramming efficiency and iPSC quality (Table , Fig. ).…”

“…Relatively higher numbers of authentic-iPSCs following Vc treatment may in part be due to Vc-mediated transformation of partially reprogrammed pre-iPSCs into fully reprogrammed iPSCs (111). Furthermore, Stadtfeld et al 113,114 demonstrated that Vc treatment substantially improved the quality of iPSCs, reviving full developmental potential and unaltered genomic status (112). Generally, OSKM-transduced miPSCs bear altered epigenetic signatures at the imprinted Dlk1-Dio3 gene locus which modulates their ability to generate iPSC-derived adult mice through tetraploid complementation.…”

“…However, supplementing reprogramming media with Vc restores H3 lysine 4 trimethylation at Dlk1-Dio3 loci of the OSKM-iPSCs, reviving full pluripotency (112). Also, supplementing reprogramming media with antioxidants, such as N-acetyl-cysteine (NAC), can substantially reduce genomic instability of iPSCs, one serious side effect of pluripotency reprogramming (113,114). NAC tends to inhibit rapid build-up of reactive oxygen species and reduces de novo copy number variations in OSKM-iPSCs, due to metabolic shift during early phases of the reprogramming (113).…”

Concise Review: Genomic Instability in Human Stem Cells: Current Status and Future Challenges

“…In line with these findings, hiPSCs also seem to form teratomas faster and with higher aggressiveness than hESCs, irrespective of the site of administration or engraftment . Two new studies have observed that mitigation of oxidative stress during reprogramming and early passaging by using antioxidant supplements in the growth media was able to reduce genome instability in hiPSCs .…”