Targeting Arterial Dysfunction in Cardiovascular Disease Using Stem Cell‐Based Therapies

Arterial regeneration represents a critical frontier in cardiovascular medicine, as progressive endothelial dysfunction, maladaptive vascular smooth muscle cell (SMC) plasticity, and chronic inflammation drive atherosclerosis, restenosis, and vascular aging. Although current therapies such as pharmacological risk-modifying therapies and interventional revascularization procedures mitigate the risk and delay the progression, they are still unable to restore vascular integrity. Stem cell-based strategies were initially conceived to replace the lost vascular cells directly; however, accumulating evidence indicates their therapeutic benefits arise from paracrine mechanisms including regulation of endothelial repair, modulation of SMC phenotypic switching, and attenuation of inflammatory signaling. This paradigm shift has expanded the regenerative landscape to encompass endothelial progenitor cells, mesenchymal stromal cells, induced pluripotent stem cell-derived vascular lineages, and engineered extracellular vesicle platforms. Parallel advances in biomaterials, mechanically tuned scaffolds, and hybrid cell-matrix constructs provide more physiologic microenvironments for vascular repair and enhance the retention, potency, and safety of regenerative therapies. Concurrently, gene editing, metabolic reprogramming, and hypoxic preconditioning further refine the functional capacity of stem cell-derived products, enabling targeted correction of endothelial instability and improving regulation of vascular remodeling. Integration of multi-omic profiling and high-resolution vascular phenotyping now positions the field to align regenerative strategies with patient-specific determinants of disease. This review integrates current knowledge on stem cell-mediated endothelial regeneration, SMC phenotype regulation, and bioengineered vascular interventions, and examines emerging precision-medicine frameworks poised to guide next-generation therapies that link mechanistic principles with translational progress to enable durable restoration of arterial structure and function, and long-term vascular health, thereby providing a theoretical basis for future research.