Clonal Mesenchymal Stem Cell-Derived Extracellular Vesicles Improve Mouse Model of Weight Drop-Induced Traumatic Brain Injury Through Reducing Cistauosis and Apoptosis Publisher Pubmed



Amini A¹ ; Shekari F^{2, 3} ; Assar Kashani S² ; Eslami N² ; Nazari A^{2, 3} ; Tofigh N⁴ ; Shahpasand K⁵ ; Akbari Javar H^{6, 7} ; Baharvand H^{2, 8}
Source: Experimental Neurology Published:2023

Abstract

Objective: Traumatic brain injury (TBI) is a major risk factor for disabilities globally with no effective treatment thus far. Recently, homogenous population of clonal mesenchymal stem cells (cMSC) and their derived extracellular vesicles (cMSC-EVs) have been proposed as a promising TBI treatment strategy. We herein investigated possible therapeutic effect of cMSC-EVs in TBI treatment and the underlying mechanisms considering cis p-tau as an early hallmark of TBI. Methods: We examined the EVs morphology, size distribution, marker expression, and uptake. Moreover, the EVs neuroprotective effects were studied in both in-vitro and in-vivo model. We also examined the anti-cis p-tau antibody-loading characteristics of the EVs. We treated TBI mouse model with EVs; prepared from cMSC-conditioned media. TBI mice were given cMSC-EVs intravenously and their cognitive functions were analyzed two months of the treatment. We employed immunoblot analysis to study the underlying molecular mechanisms. Results: We observed a profound cMSC-EVs uptake by primary cultured neurons. We found a remarkable neuroprotective effect of cMSC-EVs upon nutritional deprivation stress. Furthermore, cMSC-EVs were effectively loaded with an anti-cis p-tau antibody. There was a significant improvement in cognitive function in TBI animal models treated with cMSC-EVs compared to the saline-treated group. There was a decreased cis p-tau and cleaved caspase3 as well as increased p-PI3K in all treated animals. Conclusions: The results revealed that cMSC-EVs efficiently improved animal behaviors after TBI by reducing cistauosis and apoptosis. Moreover, the EVs can be employed as an effective strategy for antibody delivery during passive immunotherapy. © 2023 Elsevier Inc.