title: Polyphenols suppress hydrogen peroxide-induced oxidative stress in human bone-marrow derived mesenchymal stem cells.
abstract: 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.
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
authors.forename: Haruyo
authors.initials: H
authors.lastname: Yagi
authors.forename: Jian
authors.initials: J
authors.lastname: Tan
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D001713:Biphenyl Compounds / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004249:DNA Damage; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010851:Picrates / Q000378:metabolism; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D010851:Picrates; D059808:Polyphenols; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D002392:Catechin; D006861:Hydrogen Peroxide; C045651:epigallocatechin gallate; C004931:1,1-diphenyl-2-picrylhydrazyl; D002374:Catalase; D005979:Glutathione Peroxidase; D003474:Curcumin