Application of Wharton’s Jelly Mesenchymal Stem Cells in Critical Limb Ischemia

Peripheral artery disease (PAD) is a chronic vascular condition, and patients in the advanced stages typically do not respond favorably to interventional or surgical approaches. Recent advancements in Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) fundamental research have produced promising data in the context of PAD management. As recent pilot studies have suggested WJ-MSCs efficacy in patients with end-stage PAD who lack alternative treatment option, WJ-MSCs may offer a novel therapeutic strategy for managing end-stage PAD. The abundance, ease of isolation, and absence of ethical concerns associated with WJ-MSCs facilitate their potential clinical use. However, randomized, appropriately powered clinical trials are necessary to comprehensively assess their safety and effectiveness. This review aims to summarize the molecular and cellular mechanisms underlying the emerging role of WJ-MSCs in critical limb ischemia. Clinical Impact This review establishes Wharton’s Jelly MSCs (WJ-MSCs) as a paradigm-shifting therapy for end-stage critical limb ischemia (CLI).This review pioneers a translational roadmap for WJ-MSCs in CLI by integrating molecular mechanisms, preclinical models, and clinical outcomes. It uniquely identifies anatomic sourcing heterogeneity as a critical efficacy variable and proposes combination therapy with revascularization.