Stem cell-based strategies for vascular aging: from mechanistic insights to clinical translation

Vascular aging serves as a key driver of cardiovascular diseases, contributing significantly to the increasing global burden of morbidity and mortality. During vascular aging, stem cell senescence perturbs vascular homeostasis through impaired regeneration, increased oxidative stress, and chronic inflammation. Ultimately, it accelerates the development of vascular pathologies, such as atherosclerosis and aneurysm formation. This review aims to elucidate the roles of senescent vascular stem cells in the progression of vascular aging and also to explore the therapeutic potential of stem cell-based interventions in the management of cardiovascular diseases. It comprehensively includes various stem cell types, as well as their derived substances, elaborating on their roles in vascular aging and repair. Centered on "vascular stem cell senescence", it systematically elucidates the causal relationships among stem cell senescence, vascular homeostasis disruption, and the development of cardiovascular diseases, thereby constructing a focused and coherent mechanistic framework for understanding the pathological process of vascular aging. By integrating cross-system factors, including gut microbiota dysbiosis, renin-angiotensin system dysregulation, and abnormal hemodynamics, this review reveals the multi-system interactions underlying vascular aging. Moreover, it emphasizes translational rigor by not only introducing preclinical advancements but also objectively analyzing technical bottlenecks and clinical limitations, and further pointing out directions for future research. Overall, this review clarifies the roles of senescent vascular stem cells in vascular aging and the therapeutic potential of stem cell-based interventions for cardiovascular diseases, providing valuable references for promoting the clinical translation of stem cell-based strategies in the management of vascular aging-related cardiovascular diseases.