Background: Autologous cell therapy represents a novel treatment option for vascular
regeneration in different disease conditions, with experimental and clinical studies indicating a therapeutic
potential for proangiogenic cells (PCs), including endothelial progenitor cells, in the treatment of
coronary and peripheral artery disease.
Objective: To provide a summary of the therapeutic potential of PCs administration or mobilization in
peripheral artery disease, ischemic heart and cerebrovascular diseases, diabetic microvascular complications
and inflammatory rheumatic diseases.
Methods: We undertook a search of bibliographic databases for peer-reviewed research literature on the
role of PCs in vascular regeneration in preclinical and clinical models.
Results: Improvement of ischemic symptoms has been reported in different trials evaluating PCs for the
treatment of critical limb ischemia. However, in this setting, contrasting results from meta-analyses
question the long-term clinical efficacy of PC-based approaches. Preclinical studies and clinical trials
support the safety and feasibility of PC therapy in the treatment of ischemic heart and cerebrovascular
diseases, while evidence indicating a benefit on hard clinical outcomes is uncertain. Despite accumulating
experimental results support a therapeutic role for PCs in diabetic retinopathy, results from randomized
clinical trials are lacking. Whether PC therapy may limit premature atherosclerosis and reduce cardiovascular
risk in inflammatory rheumatic diseases needs to be investigated.
Conclusion: Although the potential clinical applications of PCs are accumulating, there is also evidence
of multiple limitations for autologous PC therapy. Thus, novel strategies aimed at improving PC
viability and angiogenic function are warranted in order to improve the efficacy of cell therapy