Transplantation of<i>ex vivo</i>expanded endothelial progenitor cells for therapeutic neovascularization

TLDR

Animal and early human studies indicate that angiogenic cytokines can reduce lower‑extremity and myocardial ischemia, yet the resident endothelial cell pool may constrain the extent of neovascularization. We transplanted ex vivo expanded human endothelial progenitor cells into athymic nude mice with hindlimb ischemia. Transplantation of ex vivo expanded hEPCs markedly improved blood flow, increased capillary density, and lowered limb‑loss rates, supporting their use as a supply‑side approach to therapeutic neovascularization.

Abstract

Animal studies and preliminary results in humans suggest that lower extremity and myocardial ischemia can be attenuated by treatment with angiogenic cytokines. The resident population of endothelial cells that is competent to respond to an available level of angiogenic growth factors, however, may potentially limit the extent to which cytokine supplementation enhances tissue neovascularization. Accordingly, we transplanted human endothelial progenitor cells (hEPCs) to athymic nude mice with hindlimb ischemia. Blood flow recovery and capillary density in the ischemic hindlimb were markedly improved, and the rate of limb loss was significantly reduced. Ex vivo expanded hEPCs may thus have utility as a “supply-side” strategy for therapeutic neovascularization.