title: SIRT1-dependent anti-senescence effects of cell-deposited matrix on human umbilical cord mesenchymal stem cells.
abstract: Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are considered an attractive cell source for tissue regeneration. However, environmental oxidative stress can trigger premature senescence in MSCs and thus compromises their regenerative potential. Extracellular matrix (ECM) derived from MSCs has been shown to facilitate cell proliferation and multi-lineage differentiation. This investigation evaluated the effect of cell-deposited decellularized ECM (DECM) on oxidative stress-induced premature senescence in UC-MSCs. Sublethal dosages of H2O2, ranging from 50 μm to 200 μm, were used to induce senescence in MSCs. We found that DECM protected UC-MSCs from oxidative stress-induced premature senescence. When treated with H2O2at the same concentration, cell proliferation of DECM-cultured UC-MSCs was twofold higher than those on standard tissue culture polystyrene (TCPS). After exposure to 100 μm H2O2, fewer senescence-associated β-galactosidase-positive cells were observed on DECM than those on TCPS (17.6  ±  4.0% vs. 60.4  ±  6.2%). UC-MSCs cultured on DECM also showed significantly lower levels of senescence-related regulators, such as p16INK4αand p21. Most importantly, DECM preserved the osteogenic differentiation potential of UC-MSCs with premature senescence. The underlying molecular mechanisms involved the silent information regulator type 1 (SIRT1)-dependent signalling pathway, confirmed by the fact that the SIRT1 inhibitor nicotinamide counteracted the DECM-mediated anti-senescent effect. Collagen type I, rather than fibronectin, partially contributed to the protective effect of decellularized matrix. These findings provide a new strategy of using stem cell-deposited matrix to overcome the challenge of cellular senescence and to facilitate the clinical application of MSCs in regenerative medicine. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|Departments of Biology and Chemistry, Faculty of Science, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Si
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|Department of Biology, Faculty of Science, University of Waterloo, Waterloo, ON, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Jargstorf
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Mao
authors.initials: M
authors.lastname: Li
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Pan
authors.affiliation: School of Engineering, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Zong-Ping
authors.initials: ZP
authors.lastname: Luo
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics and Division of Exercise Physiology, West Virginia University, Morgantown, WV, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Pei
authors.affiliation: Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.|Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: He
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009536:Niacinamide / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000378:metabolism*; D014470:Umbilical Cord / Q000166:cytology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D009536:Niacinamide; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D056564:Sirtuin 1
keywords: SIRT1; collagen type I; decellularization; extracellular matrix; mesenchymal stem cells; osteogenesis; oxidative stress; premature senescence