Advances in Cell-based therapies for peripheral arterial disease.

PURPOSE: To examine recent advances in cell-based therapies for peripheral arterial disease (PAD), focusing on mechanisms of action, clinical applications, and regulatory considerations. The review aimed to evaluate the therapeutic potential of various cell types and assess their efficacy in addressing the unmet needs of PAD patients,particularly those with critical limb ischemia (CLI).

METHODS

The review analysed current literature on cell-based therapies for PAD, including preclinical studies using animal models, clinical trials from phase I to III, and regulatory frameworks. Multiple cell types were evaluated, including mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), bone marrow mononuclear cells (BMMNCs),and adipose-derived stem cells (ADSCs).

RESULTS

Preclinical studies demonstrated significant improvements in limb perfusion and neovascularization across various cell types. Clinical trials, particularly those utilizing MSCs and BM-MNCs, showed encouraging outcomes in wound healing and reduced amputation rates. The therapeutic effects were mediated through multiple mechanisms, including direct vessel formation, paracrine signalling, immunomodulation, and tissue repair. The FDA's implementation of a tiered, risk-based system for human cells, tissues, and cellular and tissue-based products (HCT/Ps) has provided a regulatory framework balancing innovation with safety.

CONCLUSION

Cell-based therapies show promising potential for PAD treatment, particularly for patients with limited conventional treatment options. While clinical trials demonstrate encouraging results, challenges remain in standardizing cell characterization methods and establishing appropriate potency assays. Future research should focus on optimizing cell delivery methods, identifying the most effective cell types, and conducting larger clinical trials to establish definitive efficacy.