PMID- 33073684
OWN - NLM
STAT- MEDLINE
DCOM- 20210423
LR  - 20210423
IS  - 1544-0591 (Electronic)
IS  - 0022-0345 (Linking)
VI  - 100
IP  - 3
DP  - 2021 Mar
TI  - Extracellular Vesicles of GMSCs Alleviate Aging-Related Cell Senescence.
PG  - 283-292
LID - 10.1177/0022034520962463 [doi]
AB  - 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 
      beta-galactosidase, p21, p53, and gammaH2AX, 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 alpha 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.
FAU - Shi, H Z
AU  - Shi HZ
AD  - Department of Oral and Maxillofacial Surgery and Pharmacology, University of 
      Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
AD  - Health Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
FAU - Zeng, J C
AU  - Zeng JC
AD  - Department of Oral and Maxillofacial Surgery and Pharmacology, University of 
      Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
AD  - Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and 
      Translational Research, Guangdong Provincial Key Laboratory of Medical Molecular 
      Diagnostics, Guangdong Medical University, Dongguan, China.
FAU - Shi, S H
AU  - Shi SH
AD  - Department of Oral and Maxillofacial Surgery and Pharmacology, University of 
      Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
FAU - Giannakopoulos, H
AU  - Giannakopoulos H
AD  - Department of Oral and Maxillofacial Surgery and Pharmacology, University of 
      Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
AD  - Department of Oral & Maxillofacial Surgery, Penn Medicine Hospital of the 
      University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, 
      PA, USA.
FAU - Zhang, Q Z
AU  - Zhang QZ
AD  - Department of Oral and Maxillofacial Surgery and Pharmacology, University of 
      Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
FAU - Le, A D
AU  - Le AD
AD  - Department of Oral and Maxillofacial Surgery and Pharmacology, University of 
      Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
AD  - Department of Oral & Maxillofacial Surgery, Penn Medicine Hospital of the 
      University of Pennsylvania, Perelman Center for Advanced Medicine, Philadelphia, 
      PA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201017
PL  - United States
TA  - J Dent Res
JT  - Journal of dental research
JID - 0354343
SB  - IM
MH  - Aging
MH  - Animals
MH  - Cellular Senescence
MH  - *Extracellular Vesicles
MH  - Fibroblasts
MH  - *Mesenchymal Stem Cells
MH  - Mice
OTO - NOTNLM
OT  - endothelial cells
OT  - fibroblasts
OT  - mTOR
OT  - mesenchymal stem cells
OT  - oxidative stress
OT  - skin aging
EDAT- 2020/10/20 06:00
MHDA- 2021/04/24 06:00
CRDT- 2020/10/19 08:39
PHST- 2020/10/20 06:00 [pubmed]
PHST- 2021/04/24 06:00 [medline]
PHST- 2020/10/19 08:39 [entrez]
AID - 10.1177/0022034520962463 [doi]
PST - ppublish
SO  - J Dent Res. 2021 Mar;100(3):283-292. doi: 10.1177/0022034520962463. Epub 2020 Oct 
      17.