Potency of endothelial progenitor cells compared to bone marrow mononuclear cells in the restoration of angiogenesis

Abstract

Bone‐marrow mononuclear cells (BMMCs) have been shown to promote angiogenesis, and clinical trials suggest BMMC‐based cell therapy may be feasible for treating ischemic disease. However, recent data suggests that the presence of underlying disease states may affect the benefit of autologous BMMC‐based therapy. We previously demonstrated that direct delivery of BMMCs from SS/Mcwi rat donors failed to rescue angiogenesis in the angiogenesis impaired SS/Mcwi rat, while replacement of chromosome 13 derived from the Brown Norway rat (SS‐ 13BN/Mcwi) rat restored the angiogenic competency of BMMCs in the SS/Mcwi recipients. In this study, we performed a direct comparison of the generally pro‐angiogenic endothelial progenitor cells (EPCs) isolated from BMMCs of either SS/Mcwi or SS‐ 13BN/Mcwi donor rats. EPCs were injected into the stimulated tibialis anterior muscle of SS/Mcwi rats. Vessel density was evaluated in unstimulated and stimulated muscles after 7 days of electrical stimulation. There were no differences in the angiogenic potential of EPCs from SS‐13BN/Mcwi compared to SS/Mcwi rats. Direct injection of as few as five‐hundred EPCs was sufficient to restore angiogenesis in SS/Mcwi recipients. SS‐13BN/Mcwi EPCs were slightly more potent than SS/Mcwi EPCs in restoring the response. These data suggest that EPCs provide a more viable therapeutic approach than BMMCs to treat a variety of ischemic diseases.