Effects of Vitamin C on Cytotherapy-Mediated Muscle Regeneration

Abstract

Skeletal muscles are the largest organs in the human body, and several therapeutic trials have been conducted that included stem cell transplantation to regenerate damaged or wasted muscles. It is well known that it is essential to make a favorable microenvironment (stem cell niche) to induce the proper differentiation of the transplanted stem cells. Some drugs, such as losartan (angiotensin II type I blocker), enhance the therapeutic effects of transplanted stem cells by inhibiting fibrosis. In this study, we hypothesized that another substance, vitamin C (ascorbic acid), might improve the niche for stem cell transplantation based on its potent antioxidant effects. In both gross and microscopic observations, vitamin C-depleted mice exhibited more incomplete regeneration of damaged muscles than those treated with vitamin C. Carbonylated protein groups, which are the end products of oxidative stress, were detected in all experimental groups; however, the vitamin C-depleted groups exhibited a more potent positive reaction than that of the vitamin C-supplied groups. The difference is clearer in the presence of transplanted stem cells. Moreover, the serum total vitamin C level and the ascorbic acid (AA) to dehydroascorbic acid (DHA) ratio also were decreased in the presence of transplanted adipose-derived stem cells (ASCs). Taken together, these data can be considered as proof of vitamin C utilization by cells in vivo. The vitamin C-supplied groups displayed more severe fibrosis than that of the vitamin C-depleted groups. Since vitamin C is a major cofactor for the collagen synthesis, its deficiency resulted in reduced fibrosis. In conclusion, we demonstrated that vitamin C not only has a positive effect on adjusting the stem cell niche to boost muscle regeneration but also has an adverse aspect due to its profibrotic effect.

Vitamin C Improves Therapeutic Effects of Adipose-derived Stem Cell Transplantation in Mouse Tendonitis Model

“…Previous studies have revealed that vitamin C promoted tendon healing by stimulating extracellular matrix remodeling as a precursor of collagen synthesis (18,19). In addition, vitamin C increased the therapeutic effects of combination stem cell therapy in a muscle laceration model (20). However, there has been no study as far as we are aware on the therapeutic effects of combination stem cell therapy and vitamin C administration on tendinopathy.…”

“…However, there has been no study on co-administration of stem cell therapy with a particular compound (e.g. vitamin C or losartan) known to improve the stem cell niche in tendinopathy (20,31). The aim of this study was to determine the combined effects of stem cell therapy and vitamin C in the treatment of tendinopathy.…”

“…The results indicated that vitamin C increased the effect of stem cells in tendon healing. In addition, a previous study reported that vitamin C supported cell transplantation by preventing oxidative stress (20).…”

Vitamin C enhances the ex vivo proliferation of porcine muscle stem cells for cultured meat production

“…20,21 Recent studies also demonstrate that VC is associated with epigenetic reprogramming [22][23][24] and muscle regeneration. [25][26][27] Besides, VC has been widely used in the ex vivo culture of various cell types such as cardiac progenitor cells, 28 osteoblasts, 29 and induced pluripotent stem cells. 30 However, the effect of VC on the ex vivo proliferation and differentiation of MuSCs has not been well understood.…”

Effect of ascorbic acid on collagen and some inflammatory mediators in rats

“…In a study that investigated the effect of AA deficiency on skeletal muscle in senescence marker protein-30 knockout mice, it was found that the cross-sectional area of muscle was significantly smaller in the AA deficiency group compared with the AA-treated group (1.5 g/L) (25). In the animal study that examined the effect of vitamin C on muscle renewal in the case of cytotherapy, it was observed that vitamin C enhanced muscle tissue collagen type I expression (17). However, in our study, AA administration did not show a significant effect on collagen type I levels at the dose and time administered.…”