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Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stromal Cells Protect Cardiac Cells Against Hypoxia/Reoxygenation Injury by Inhibiting Endoplasmic Reticulum Stress via Activation of the PI3K/Akt Pathway.

Authors
  • Zhang, Changyi1
  • Wang, Hongwu2
  • Chan, Godfrey C F3
  • Zhou, Yu4
  • Lai, Xiulan5
  • Lian, Ma2, 6
  • 1 Department of Cardiology, 74599Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China. , (China)
  • 2 Department of Pediatrics, 74599Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China. , (China)
  • 3 Department of Adolescent Medicine, 26473Queen Mary Hospital, Hong Kong, PR China. , (China)
  • 4 Department of Neurology, 74599Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China. , (China)
  • 5 Department of Pediatrics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong, PR China. , (China)
  • 6 Department of Hematology and Oncology, 85113Shenzhen Children's Hospital, Shenzhen, Guangdong, PR China. , (China)
Type
Published Article
Journal
Cell Transplantation
Publisher
SAGE Publications
Publication Date
Jan 01, 2020
Volume
29
Identifiers
DOI: 10.1177/0963689720945677
PMID: 32864999
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Endoplasmic reticulum (ER) stress is implicated in the pathogenesis of many diseases, including myocardial ischemia/reperfusion injury. We hypothesized that human umbilical cord mesenchymal stromal cells derived extracellular vesicles (HuMSC-EVs) could protect cardiac cells against hyperactive ER stress induced by hypoxia/reoxygenation (H/R) injury. The H/R model was generated using the H9c2 cultured cardiac cell line. HuMSC-EVs were extracted using a commercially available exosome isolation reagent. Levels of apoptosis-related signaling molecules and the degree of ER stress were assessed by western blot. The role of the PI3K/Akt pathway was investigated using signaling inhibitors. Lactate dehydrogenase leakage and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) analysis were used for evaluating the therapeutic effects of HuMSC-EVs in vitro. The results showed that ER stress and the rate of apoptosis were increased in the context of H/R injury. Treatment with HuMSC-EVs inhibited ER stress and increased survival in H9c2 cells exposed to H/R. Mechanistically, the PI3K/Akt pathway was activated by treatment with HuMSC-EVs after H/R. Inhibition of the PI3K/Akt pathway by a specific inhibitor, LY294002, partially reduced the protective effect of HuMSC-EVs. Our findings suggest that HuMSC-EVs could alleviate ER stress-induced apoptosis during H/R via activation of the PI3K/Akt pathway.

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