Study on the Mechanism of Bone Marrow Stem Cell-Derived Exosome miR-30a/DLL4 Acting on Traumatic Brain Injury Angiogenesis.

OBJECTIVE

To explore the effects of bone marrow stem cell (BMSC)-derived exosome miR-30a/DLL4 expression on angiogenesis following traumatic brain injury (TBI), which may provide a novel therapeutic strategy for postoperative TBI recovery.

METHODS

A rat TBI model was established using the free-fall method, and exosomes from different sources were injected into the brain. Rats were divided into sham-operated, TBI model, TBI+inhibitor NC-Exo, TBI+miR-30a-inhibitor-Exo, TBI+OE NC-Exo, and TBI+DLL4-OE-Exo groups. Neurological function was assessed using mNSS and water maze tests. H&E staining, immunohistochemistry (CD31, CD34, GFAP, NSE, DLL4, VEGF), and qPCR (miR-30a-5p, DLL4, VEGF mRNA) were performed to evaluate angiogenesis and neurorepair.

RESULTS

Hematoxylin and eosin staining confirmed successful TBI modeling, with reduced neurons and pathologic changes in the injury foci. Exosomes with low miR-30a-5p and high DLL4 expression alleviated TBI pathology and improved neurological function. qPCR showed that miR-30a-5p downregulation and DLL4 upregulation reduced VEGFA expression. Immunohistochemistry revealed low CD31, CD44, and VEGFA, and high DLL4, GFAP, and NSE in the TBI model. BMSC exosome treatment upregulated vascular markers (CD31, CD44, and VEGFA) and downregulated injury markers (GFAP and NSE), effects reversed by miR-30a-5p inhibition and DLL4 overexpression.

CONCLUSION

Bone marrow stem cell exosomes promote post-TBI angiogenesis and nerve function recovery, partially through the regulation of miR-30a-5p and DLL4 expression. These findings suggest that BMSC-derived exosomes may offer a novel therapeutic strategy for TBI and craniofacial trauma. For surgeons, this study provides a preclinical foundation for developing exosome-based intraoperative adjuvants to enhance vascularization in trauma sites, thereby improving graft survival in reconstructive surgery and reducing postoperative complications such as ischemia-reperfusion injury.