Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
J Cell Biochem. 2013 May;114(5):1163-73. doi: 10.1002/jcb.24459.
Human mesenchymal stem cells (hMSCs) are considered a highly promising candidate cell type for cell-based tissue engineering and regeneration because of their self-renewal and multi-lineage differentiation characteristics. Increased levels of reactive oxygen/nitrogen species (ROS/RNS) are associated with tissue injury and inflammation, impact a number of cellular processes, including cell adhesion, migration, and proliferation, and have been linked to cellular senescence in MSCs, potentially compromising their activities. Naturally occurring polyphenolic compounds (polyphenols), epigallocatechin-3-gallate (EGCG), and curcumin, block ROS/RNS and are potent inflammation-modulating agents. However, their potential protective effects against oxidative stress in hMSCs have not been examined. In this study, we carried out a systematic analysis of the effects of polyphenols on hMSCs in their response to oxidative stress in the form of treatment with H(2)O(2) and S-nitroso-N-acetylpenicillamine (SNAP), respectively. Parameters measured included colony forming activity, apoptosis, and the levels of antioxidant enzymes and free reactive species. We found that polyphenols reversed H(2)O(2) -induced loss of colony forming activity in hMSCs. In a dose-dependent manner, polyphenols inhibited increased levels of ROS and NO, produced by H(2)O(2) or SNAP, respectively, in MSCs. Notably, polyphenols rapidly and almost completely blocked H(2)O(2) -induced ROS in the absence of significant direct effect on H(2)O(2) itself. Polyphenols also protected the antioxidant enzymes and reduced apoptotic cell death caused by H(2)O(2) exposure. Taken together, these findings demonstrate that EGCG and curcumin are capable of suppressing inducible oxidative stress in hMSCs, and suggest a possible new approach to maintain MSC viability and potency for clinical application.
人骨髓间充质干细胞（hMSCs）因其自我更新和多能性分化特性，被认为是细胞基组织工程和再生的极有前途的候选细胞类型。活性氧/氮物种（ROS/RNS）水平升高与组织损伤和炎症有关，影响包括细胞黏附、迁移和增殖在内的许多细胞过程，并与 MSCs 中的细胞衰老有关，可能会损害其功能。天然存在的多酚化合物（多酚）、表没食子儿茶素-3-没食子酸酯（EGCG）和姜黄素可以阻断 ROS/RNS，是有效的炎症调节药物。然而，它们在 hMSCs 中对抗氧化应激的潜在保护作用尚未得到检验。在这项研究中，我们系统地分析了多酚在 hMSCs 对 H2O2 和 S-亚硝基-N-乙酰青霉胺（SNAP）形式的氧化应激的反应中的作用。测量的参数包括集落形成活性、凋亡和抗氧化酶和游离反应性物质的水平。我们发现多酚逆转了 H2O2 诱导的 hMSCs 集落形成活性丧失。多酚以剂量依赖的方式抑制了 H2O2 或 SNAP 分别产生的 ROS 和 NO 水平的升高。值得注意的是，多酚在没有对 H2O2 本身产生显著直接作用的情况下，迅速且几乎完全阻断了 H2O2 诱导的 ROS。多酚还保护抗氧化酶并减少由 H2O2 暴露引起的细胞凋亡。总之，这些发现表明 EGCG 和姜黄素能够抑制 hMSCs 中的诱导性氧化应激，并为维持 MSC 活力和用于临床应用提供了一种新的可能方法。
