Background: Wound healing is a complex biological process involving vascular remodeling and tissue repair. However, the mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) facilitates vascular maturation during wound healing remains unclear. This study aims to investigate the biological mechanism by which GM-CSF promotes vascular maturation and enhances wound repair.
Methods: Human dermal microvascular endothelial cells (ECs) and human brain vascular pericytes (PCs) were cultured separately or in co-culture and treated with various concentrations of GM-CSF. Cell proliferation and migration were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylformazan and Transwell assays. Tube formation assays were performed to evaluate angiogenic potential. The expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot. Endothelial permeability was analyzed using fluorescein isothiocyanate (FITC)-dextran staining. The expression of platelet endothelial cell adhesion molecule 1 (PECAM-1) was assessed by immunofluorescence.
Results: GM-CSF substantially raised EC and PC proliferation and migration in a dose-dependent manner, with more pronounced effects observed in co-culture conditions. GM-CSF grew VEGF and Ang-1 in PCs and enhanced tube formation and barrier integrity in both mono- and co-cultured ECs. Furthermore, GM-CSF-stimulated PC-conditioned medium induced the upregulation of PECAM-1 in ECs.
Conclusion: GM-CSF promotes PECAM1 expression, angiogenesis, and vascular maturation in ECs by upregulating VEGF and Ang-1 in PCs. These effects enhance the interaction between endothelial cells and pericytes, thereby contributing to vascular stabilization and improved wound healing.
Exosomes, a specialized class of extracellular vesicles, exhibit significant therapeutic potential for neurological disorders. In particular for vascular dementia (VaD), the second most common form of dementia. VaD is characterized by cognitive and behavioral impairments, often linked to hippocampal damage resulting from its vulnerable vascular structure, which disrupts memory formation and retrieval. Secreted by various cell types within the central nervous system, exosomes mediate intercellular communication by transporting bioactive molecules. Growing evidence indicates that exosomes enhance synaptic plasticity, modulate neuroinflammation, inhibit apoptosis, and promote angiogenesis, supporting their therapeutic potential in VaD. Given the urgent need for effective treatments and the unique ability of exosomes to cross the blood-brain barrier (BBB) and deliver multi-targeted therapies, research in this field is critically important. It offers a viable pathway toward the development of disease-modifying interventions for a condition that is currently managed primarily through symptomatic treatment. This review summarizes current knowledge on the function of exosomes in the central nervous system, examines recent advances in exosome-based strategies for VaD, and discusses ongoing challenges and future directions for their clinical translation.

