Therapeutic Neovascularization By Transplantation Of Mobilized Peripheral Blood Mononuclear Cells For Limb Ischemia

Objective Autolougous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized human peripheral blood mononuclear cells (PBMNCs) improves limb ischemia in patients with arteriosclerosis obliterans of lower extremities and with diabetic foot. However, the mechanism of action of PBMNCs remains elusive. The present study was designed to investigate the role of CD34~+ stem/progeitor cells in neovascularization by comparing the therapeutic effects of G-CSF-mobilized PBMNCs and CD34-depleted G-CSF-mobilized PBMNCs transplantation in ischemic hindlimbs of nude mice. We also tried to reveal the mechanisms of action through which the transplanted cells effectively acted in vivo in improving critical limb ischemia Methods. Peripheral blood leukapheresis products were obtained from healthy volunteers who received subcutaneous administration of G-CSF. Mononuclear cells were separately isolated from the human products of leukapheresis by Ficoll-Paque density gradient centrifugation. The G-CSF-mobilized PBMNCs were divided into two parts. One part was the G-CSF-mobilized PBMNCs and the other part was CD34-depleted...