Resveratrol Exerts Dosage and Duration Dependent Effect on Human Mesenchymal Stem Cell Development

Abstract

Studies in the past have illuminated the potential benefit of resveratrol as an anticancer (pro-apoptosis) and life-extending (pro-survival) compound. However, these two different effects were observed at different concentration ranges. Studies of resveratrol in a wide range of concentrations on the same cell type are lacking, which is necessary to comprehend its diverse and sometimes contradictory cellular effects. In this study, we examined the effects of resveratrol on cell self-renewal and differentiation of human mesenchymal stem cells (hMSCs), a type of adult stem cells that reside in a number of tissues, at concentrations ranging from 0.1 to 10 µM after both short- and long-term exposure. Our results reveal that at 0.1 µM, resveratrol promotes cell self-renewal by inhibiting cellular senescence, whereas at 5 µM or above, resveratrol inhibits cell self-renewal by increasing senescence rate, cell doubling time and S-phase cell cycle arrest. At 1 µM, its effect on cell self-renewal is minimal but after long-term exposure it exerts an inhibitory effect, accompanied with increased senescence rate. At all concentrations, resveratrol promotes osteogenic differentiation in a dosage dependent manner, which is offset by its inhibitory effect on cell self-renewal at high concentrations. On the contrary, resveratrol suppresses adipogenic differentiation during short-term exposure but promotes this process after long-term exposure. Our study implicates that resveratrol is the most beneficial to stem cell development at 0.1 µM and caution should be taken in applying resveratrol as an anticancer therapeutic agent or nutraceutical supplement due to its dosage dependent effect on hMSCs.

Determination of trans-resveratrol action on two different types of neuronal cells, neuroblastoma and hippocampal cells

“…The metabolic properties of cancer cells are remarkably different from those of normal cells (Zhao et al 2013). Cells with higher rates of metabolism are more sensitive to the actions of polyphenols and oxidising factors as well (Peltz et al 2012). Furthermore, a point that must always be borne in mind is that effects may change a "sign" depending on the concentration.…”

“…They claimed that resveratrol's functional discrepancies appear to have resulted from different cells being exposed to it at different concentrations in different experimental settings. Low concentrations of this polyphenol stimulate pro-survival effects in stem cells; however, higher concentrations initiate pro-death effects in cancer cell lines (Peltz et al 2012).…”

Dosage and Cell Line Dependent Inhibitory Effect of bFGF Supplement in Human Pluripotent Stem Cell Culture on Inactivated Human Mesenchymal Stem Cells

“…Passage 5–6 hMSCs cells were used in all experiments described. Multipotency of these cells was validated by independent osteogenic and adipogenic differentiation (data not shown) [50]. For mitomycin C treatment, confluent cells on 10-cm plates were treated with 10 µg/ml mitomycin C (cat# M4287, Sigma) for about 2.5 to 3 hours and washed with PBS 3 times before being used or frozen.…”

Potensi Suplementasi Resveratrol dalam Mengatasi Efek Negatif Hormon Tiroid pada Terapi Obesitas: Uji Preklinik

“…19 Pemberian RSV per oral 100 mg/kgBB/hari pada tikus Wistar mampu memperlihatkan bioavailabilitas yang rendah dengan kadar plasma 1,3 mM. 20 Pemilihan dosis 100 mg/kgBB/hari pada penelitian ini berdasarkan penelitian Aydin dkk. 8 yang mengeksplorasi efek RSV terhadap stres oksidatif pada hewan coba model sepsis Pada penelitian ini tidak dilakukan pengukuran kadar RSV dalam plasma.…”