Resveratrol exerts dosage and duration dependent effect on human mesenchymal stem cell development.
Resveratrol exerts dosage and duration dependent effect on human mesenchymal stem cell development.
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白藜芦醇对人间充质干细胞发育的剂量和持续时间依赖性作用。
DOI：
10.1371/journal.pone.0037162
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Peltz L;Gomez J;Marquez M;Alencastro F;Atashpanjeh N;Quang T;Bach T;Zhao Y
过去的研究已经阐明了白藜芦醇作为抗癌（促细胞凋亡）和延长生命（促生存）化合物的潜在益处。然而，在不同的浓度范围内观察到这两种不同的效应。白藜芦醇在相同细胞类型的广泛浓度的研究是缺乏的，这是必要的，以了解其多样性，有时矛盾的细胞效应。在这项研究中，我们研究了白藜芦醇对人类间充质干细胞（hMSCs）的细胞自我更新和分化的影响，hMSCs是一种存在于许多组织中的成体干细胞，浓度范围为0.1至10 µM。我们的研究结果表明，在0.1 μM时，白藜芦醇通过抑制细胞衰老来促进细胞自我更新，而在5 μM或更高浓度时，白藜芦醇通过增加衰老率，细胞倍增时间和S期细胞周期停滞来抑制细胞自我更新。在1 μM时，它对细胞自我更新的影响很小，但在长期暴露后，它会产生抑制作用，并伴随着衰老率的增加。在所有浓度下，白藜芦醇以剂量依赖性方式促进成骨分化，这被其在高浓度下对细胞自我更新的抑制作用所抵消。相反，白藜芦醇在短期暴露期间抑制脂肪形成分化，但在长期暴露后促进这一过程。我们的研究表明，白藜芦醇在0.1 μM时对干细胞发育最有益，由于其对hMSC的剂量依赖性作用，在将白藜芦醇用作抗癌治疗剂或营养补充剂时应谨慎。
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.
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影响因子：
3.3
作者：
Della-Morte, D.;Dave, K. R.;Defazio, R. A.;Bao, Y. C.;Raval, A. P.;Perez-Pinzon, M. A.
通讯作者：
Perez-Pinzon, M. A.
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
DOI：
10.1073/pnas.0403493101
发表时间：
2004-08-31
影响因子：
11.1
作者：
Bauer, JH;Goupil, S;Helfand, SL
通讯作者：
Helfand, SL
DOI：
10.1006/bbrc.1998.9916
发表时间：
1999-01-27
影响因子：
3.1
作者：
Carbó, N;Costelli, P;Argilés, JM
通讯作者：
Argilés, JM
影响因子：
64.8
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
Sinclair, David A.