SIRT1-dependent anti-senescence effects of cell-deposited matrix on human umbilical cord mesenchymal stem cells.

Autor: Zhou L; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China., Chen X; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou, China., Liu T; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China., Zhu C; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China., Si M; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; Departments of Biology and Chemistry, Faculty of Science, University of Waterloo, Waterloo, ON, Canada., Jargstorf J; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; Department of Biology, Faculty of Science, University of Waterloo, Waterloo, ON, Canada., Li M; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China., Pan G; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China., Gong Y; School of Engineering, Sun Yat-sen University, Guangzhou, China., Luo ZP; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China., Yang H; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China., Pei M; Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics and Division of Exercise Physiology, West Virginia University, Morgantown, WV, USA., He F; Orthopaedic Institute, Medical College, Soochow University, Suzhou, China.; Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, China.
Jazyk: angličtina
Zdroj: Journal of tissue engineering and regenerative medicine [J Tissue Eng Regen Med] 2018 Feb; Vol. 12 (2), pp. e1008-e1021. Date of Electronic Publication: 2017 Jun 20.
DOI: 10.1002/term.2422
Abstrakt: 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 H 2 O 2 , 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 H 2 O 2 at 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 H 2 O 2 , 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 p16 INK4α and 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.
(Copyright © 2017 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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