Extracellular Vesicles of GMSCs Alleviate Aging-Related Cell Senescence

• Published in: Journal of dental research Vol. 100; no. 3; pp. 283 - 292
• Main Authors: Shi, H.Z., Zeng, J.C., Shi, S.H., Giannakopoulos, H., Zhang, Q.Z., Le, A.D.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-03-2021; SAGE PUBLICATIONS, INC
• Subjects: Aging; Animals; Cell cycle; Cellular Senescence; Cyclin-dependent kinase inhibitor p21; Dentistry; Endothelial cells; Extracellular Vesicles; Fibroblasts; Homeostasis; Interleukin 6; Mesenchymal Stem Cells; Mesenchyme; Mice; Oxidative stress; p53 Protein; Rapamycin; Senescence; Signal transduction; Skin; Stem cell transplantation; TOR protein; Tumor necrosis factor-α; Umbilical vein; β-Galactosidase; mTOR; fibroblasts; endothelial cells; skin aging; mesenchymal stem cells; oxidative stress
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034520962463

Healthy aging is a complex biological process with progressive accumulation of senescent cells characterized by stable cell cycle arrest, resulting in impaired homeostasis, regenerative potential, and gradual functional decline in multiple tissues and organs, whereby the aberrant activation of mammalian target of rapamycin (mTOR) signaling networks plays a central role. Herein, we explored the effects of extracellular vesicles (EVs) released by gingiva-derived mesenchymal stem cells (GMSC-EVs) on oxidative stress–induced cellular senescence in human endothelial cells and skin fibroblasts and their antiaging potentials. Our results showed that GMSC-EVs robustly abrogated oxidative stress–induced upregulation in the expression of cellular senescence-related genes, such as β-galactosidase, p21, p53, and γH2AX, and mTOR/pS6 signaling pathway, in human umbilical vein endothelial cells (HUVECs) and skin fibroblasts. Meanwhile, GMSC-EVs restored oxidative stress–induced impairment in proliferation and tube formation by HUVECs. Systemic administration of GMSC-EVs attenuated aging-associated elevation in the expression levels of p21, mTOR/pS6, interleukin 6, and tumor necrosis factor α in skin and heart tissues of aged mice. These findings suggest that GMSC-EVs could be a potential alternative source of cell-free product for attenuation of aging-related skin and vascular dysfunctions due to their potent inhibitory effects on oxidative stress–induced cellular senescence in endothelial cells and skin fibroblasts.