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