POB.066 - Therapeutic effects of miRNAs of exosomes derived from human bone marrow mesenchymal stem cells on histological outcome in rats after traumatic brain injury
Recommended Citation
Zhang Y, Zhang Y, Chopp M, Pang H, Wang X, Lu M, Chen L, Lu M, Zhang Z, Mahmood A, Xiong Y. POB.066 - Therapeutic effects of miRNAs of exosomes derived from human bone marrow mesenchymal stem cells on histological outcome in rats after traumatic brain injury. J Neurotrauma 2025; 42(13-14):e1186.
Document Type
Conference Proceeding
Publication Date
6-12-2025
Publication Title
J Neurotrauma
Keywords
argonaute 2 protein, brain derived neurotrophic factor, caspase 3, chlordane, fibrin, fibrinogen, microRNA, neurotrophic factor, synaptophysin, tumor necrosis factor, adult, animal experiment, animal model, animal tissue, bone marrow mesenchymal stem cell, cell death, conference abstract, controlled study, exosome, histology, human, immunofluorescence, immunohistochemistry, inflammation, male, nervous system inflammation, nonhuman, rat, synaptogenesis, therapy effect, traumatic brain injury
Abstract
We previously showed that exosomes from naïve and engineered bone marrow mesenchymal stem cells (MSCs) improve functional recovery in rats after traumatic brain injury (TBI). This study examines the effects of MSC-derived exosomes with varying miRNA expression levels on histological outcomes following TBI. Young male rats with moderate TBI induced by controlled cortical impact injury (CCI) were randomly assigned to receive phosphate-buffered solution (PBS, control) or one dose of exosomes (100 lg/rat) from naïve MSCs (MSC group), MSCs overexpressing miR-17-92 (miR- 17-92 group), MSCs with an empty vector (miR-17-92-Empty group), MSCs with Argonaute 2 knockout with reduction of miRNAs (Ago2-KO group), or MSCs with an empty vector (Ago2-Vector group), administered 24 hours post-injury. Rat brains were collected 2 days post-injury for immunostaining of inflammatory markers (CD68, TNF alpha, CCR2), cell death (caspase-3), neurotrophic factors (BDNF, NGF), BBB breakdown (fibrin/fibrinogen), and synaptogenesis (Synaptophysin). Analysis of variance (ANOVA) followed by post hoc Tukey's tests was used for data analyses. PBS-treated TBI rats significantly increased neuroinflammation, cell death, and BBB damage and decreased synaptogenesis and neurotrophic factor expression in the injured brain vs Sham group (p<0.05). Treatments from MSC, miR-17-92-Empty or Ago2- Vector groups significantly decreased neuroinflammation, cell death, and BBB damage and increased synaptogenesis and neurotrophic factor expression in the injured brain vs PBS group (p<0.05). Exosomes from the miR-17-92 group provided further benefits while exosomes from the Ago2-KO group exhibited opposite effects vs MSC group (p<0.05). These results support use of engineered exosomes enriched with select miRNAs as a potential treatment for TBI.
Volume
42
Issue
13-14
First Page
e1186
