Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes

Abstract

Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)-and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

Ascorbic acid promotes cardiomyogenesis through SMAD1 signaling in differentiating mouse embryonic stem cells

“…Since the first report by Takahashi et al [ 5 ], numerous groups have documented that AA promotes CM differentiation from both mouse and human ESCs and iPSCs [ 6 , 8 , 23 , 24 ]. AA is now considered indispensable for the routine production of hPSC-CMs using defined media [ 1 ].…”

Transcriptional profiling of interleukin-2-primed human adipose derived mesenchymal stem cells revealed dramatic changes in stem cells response imposed by replicative senescence

“…Transplanted mesenchymal stem cells (MSCs) are consistently exposed to tissue signals, immune cells and mediators that could influence their behavior. The mechanisms by which this environment influences potential therapeutic outcomes in MSC clinical applications remain poorly understood, however, over the past decade MSCs themselves have been shown to possess a broad spectrum of signaling capabilities, affecting both adaptive and innate immunity by the secretion of growth factors and chemokines to induce cell proliferation, angiogenesis, interactions with the immune system and mediation of anti-apoptotic events [ 1 , 2 ]. Based on these remarkable properties, the MSCs are considered to have therapeutic potential to treat broad spectrum of diverse human diseases, including cancer [ 3 ].…”

Effects of Natural Progesterone and Synthetic Progestin on Germ Layer Gene Expression in a Human Embryoid Body Model

“…Human embryonic stem cells (hESCs) are derived from the inner cell mass of human blastocyst stage embryos [11,12]. Human embryoid bodies (hEBs) are differentiated from hESCs [13,14] and can be used as a surrogate model [15,16] since they recapitulate many differentiation processes of early human embryonic development [17][18][19]. Previously, we have reported a feasible use for hEBs as an in vitro early human developmental model [20] and other studies showed that the progestational compound affected the differentiation of hESCs and hEBs [21][22][23][24][25].…”