TSG-6 released from adipose stem cells-derived small extracellular vesicle protects against spinal cord ischemia reperfusion injury by inhibiting endoplasmic reticulum stress.


Journal

Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581

Informations de publication

Date de publication:
13 07 2022
Historique:
received: 02 09 2021
accepted: 12 06 2022
entrez: 13 7 2022
pubmed: 14 7 2022
medline: 16 7 2022
Statut: epublish

Résumé

Spinal cord ischemia reperfusion injury (SCIRI) is a complication of aortic aneurysm repair or spinal cord surgery that is associated with permanent neurological deficits. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been shown to be potential therapeutic options for improving motor functions after SCIRI. Due to their easy access and multi-directional differentiation potential, adipose-derived stem cells (ADSCs) are preferable for this application. However, the effects of ADSC-derived sEVs (ADSC-sEVs) on SCIRI have not been reported. We found that ADSC-sEVs inhibited SCIRI-induced neuronal apoptosis, degradation of tight junction proteins and suppressed endoplasmic reticulum (ER) stress. However, in the presence of the ER stress inducer, tunicamycin, its anti-apoptotic and blood-spinal cord barrier (BSCB) protective effects were significantly reversed. We found that ADSC-sEVs contain tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) whose overexpression inhibited ER stress in vivo by modulating the PI3K/AKT pathway. ADSC-sEVs inhibit neuronal apoptosis and BSCB disruption in SCIRI by transmitting TSG-6, which suppresses ER stress by modulating the PI3K/AKT pathway.

Sections du résumé

BACKGROUND
Spinal cord ischemia reperfusion injury (SCIRI) is a complication of aortic aneurysm repair or spinal cord surgery that is associated with permanent neurological deficits. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been shown to be potential therapeutic options for improving motor functions after SCIRI. Due to their easy access and multi-directional differentiation potential, adipose-derived stem cells (ADSCs) are preferable for this application. However, the effects of ADSC-derived sEVs (ADSC-sEVs) on SCIRI have not been reported.
RESULTS
We found that ADSC-sEVs inhibited SCIRI-induced neuronal apoptosis, degradation of tight junction proteins and suppressed endoplasmic reticulum (ER) stress. However, in the presence of the ER stress inducer, tunicamycin, its anti-apoptotic and blood-spinal cord barrier (BSCB) protective effects were significantly reversed. We found that ADSC-sEVs contain tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) whose overexpression inhibited ER stress in vivo by modulating the PI3K/AKT pathway.
CONCLUSIONS
ADSC-sEVs inhibit neuronal apoptosis and BSCB disruption in SCIRI by transmitting TSG-6, which suppresses ER stress by modulating the PI3K/AKT pathway.

Identifiants

pubmed: 35831906
doi: 10.1186/s13287-022-02963-4
pii: 10.1186/s13287-022-02963-4
pmc: PMC9281104
doi:

Substances chimiques

Proto-Oncogene Proteins c-akt EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

291

Informations de copyright

© 2022. The Author(s).

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Auteurs

Xiao Lu (X)

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.
Department of Orthopaedics, Dongtai Hospital Affiliated to Nantong University, Dongtai City, Jiangsu, China.

Chengtang Lv (C)

Department of Orthopaedics, Yancheng Third People's Hospital, Yancheng, 224000, Jiangsu, China.

Yuechao Zhao (Y)

Department of Orthopedic Oncology, Changzheng Hospital, Secondary Military Medical University, Shanghai, China.
Department of Orthopedic, PLA Navy No.905 Hospital, Secondary Military Medical University, Shanghai, China.

Yufei Wang (Y)

Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Haining, Zhejiang, China.

Yao Li (Y)

Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China.

Chengyue Ji (C)

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.

Zhuanghui Wang (Z)

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.

Wu Ye (W)

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China.

Shunzhi Yu (S)

Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, China. maotoutou@163.com.

Jianling Bai (J)

Department of Biostatistics, School of Public Health, Nanjing Medical University, Jiangsu Province, Nanjing, 211166, China. baijianling@njmu.edu.cn.

Weihua Cai (W)

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, China. caiweihuazhuren@163.com.

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