Cited by 100Extracellular vesicles in diseaseMesenchymal stem cell researchParkinson's Disease Mechanisms and Treatments

MSC-Derived Exosomes can Enhance the Angiogenesis of Human Brain MECs and Show Therapeutic Potential in a Mouse Model of Parkinson's Disease

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Xue, Chunling, Li, Xuechun, Ba, Li, Zhang, Mingjia, Yang, Ying, Gao, Yang, Sun, Zhao, Han, Qin +1 more·2021·Aging and disease

Abstract

Parkinson's disease (PD) is the second most widespread neurodegenerative disorder in the world. It has been reported that exosomes derived from mesenchymal stem cells (MSCs) can contribute to the recovery of PD. However, the underlying mechanism remains poorly defined. In this study, proteomics and time-series analysis showed that exosomes derived from MSCs can keep human brain microvascular endothelial cells (HBMECs) in a transcriptionally active state, which may be beneficial for angiogenesis. Next, we found that MSC-derived exosomes can promote the angiogenesis of HBMECs by increasing the expression of ICAM1, and alleviate the damage caused by 1-methyl-4-phenylpyridinium (MPP+) in these cells. Accordingly, when ICAM1 was knocked down, the tube formation ability of HBMECs was obviously decreased. In addition, ICAM1 was found to promote the angiogenesis of HBMECs by activating the SMAD3 and P38MAPK signaling pathways. In a PD mouse model, MSC-derived exosomes were found to contribute to the recovery of PD by promoting ICAM1-related angiogenesis. These findings demonstrate that the exosome-ICAM1-SMAD3/P38MAPK axis can promote the angiogenesis of HBMECs, with possible therapeutic potential for PD.

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  1. [4]Shults CW (2006). Lewy bodies. Proc Natl Acad Sci U S A, 103: 1661- 1668. 16449387 PMC1413649

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Authors
Xue, C., Li, X., Ba, L., Zhang, M., Yang, Y., Gao, Y., Sun, Z., Han, Q., & Zhao, R. C.
Affiliations
Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Corresponding author
Han, Qin
Venue
Aging and disease
Published
2021
Volume
12
Issue
5
Pages
1211
ISSN
2152-5250 (ISSN-L)
OpenAlex
W3187910293
Cited by
100
References
43
Citations by year
2026: 13 · 2025: 18 · 2024: 29 · 2023: 25 · 2022: 13 · 2021: 2
FWCI
5.42
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81700782, 111 Project, 2017-I2M-3-007, 81672313, 2016YFA0101003)
  • Higher Education Discipline Innovation Project (B18007)
  • National Key Research and Development Program of China (2017-I2M-3-007, 2016YFA0101003)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords
mesenchymal stem cell-derived exosomes, Parkinson's disease, angiogenesis, brain microvascular endothelial cells, ICAM-1, Smad3 signaling, p38 MAPK signaling, MPP+ neurotoxicity, tube formation, exosome therapy

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