The Role of Perivascular Stem Cells in Inflammatory Vascular Diseases: From Immunomodulation to Vascular Regeneration.

Inflammatory vascular diseases (including atherosclerosis, peripheral artery disease, and vasculitis) are driven by chronic vascular wall inflammation and immune cell infiltration, representing a leading cause of global mortality. Perivascular stem cells (PSCs)-an umbrella term for mesenchymal stem cells, endothelial progenitor cells, and tissue-resident CD34+ cells-have emerged as a promising therapeutic approach due to their dual capacity for immunomodulation and vascular repair. This review systematically synthesizes current evidence on three core mechanisms: immunomodulation (suppressing pathogenic T cells and reprogramming macrophages toward an anti-inflammatory phenotype), vascular repair (promoting endothelial regeneration and functional angiogenesis), and mitochondrial transfer as a recently discovered intercellular rescue pathway. We critically discuss the clinical translation landscape, including failed trials, withdrawn products, patient heterogeneity, and current regulatory positions of the FDA and EMA. Finally, we outline future directions including precision medicine, bioengineered delivery systems, and cell-free extracellular vesicle therapies. By moving from a conventional anti-inflammatory paradigm to an integrated immunomodulatory-reparative strategy, PSC-based therapies hold potential to transform the treatment of inflammatory vascular diseases.