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Clonal mesenchymal stem cell-derived extracellular vesicles improve mouse model of weight drop-induced traumatic brain injury through reducing cistauosis and apoptosis.
- Source :
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Experimental Neurology . Sep2023, Vol. 367, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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Abstract
- 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. 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. 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. 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. • Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) improved behavioral recovery after traumatic brain injury. • MSC-EVs reduced cistauosis and apoptosis after traumatic brain injury. • MSC-EVs ameliorated traumatic brain injury as effective as anti-cis p-tau antibody. [ABSTRACT FROM AUTHOR]
- Subjects :
- *BRAIN injuries
*EXTRACELLULAR vesicles
*MESENCHYMAL stem cells
*LABORATORY mice
Subjects
Details
- Language :
- English
- ISSN :
- 00144886
- Volume :
- 367
- Database :
- Academic Search Index
- Journal :
- Experimental Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 165114481
- Full Text :
- https://doi.org/10.1016/j.expneurol.2023.114467