Therapeutic angiogenesis by transplantation of autologous bone marrow and peripheral blood mononuclear cells in patients with peripheral arterial disease

Abstract

Recently, the effectiveness and safety of therapeutic angiogenesis by transplantation of autologous bone marrow mononuclear cells (BM-MNCs) to ischemic limbs have been reported. We investigated whether transplantation of peripheral blood mononuclear cells (PB-MNCs) would also be as effective as BM-MNC-transplantation in patients with peripheral arterial disease. BM-MNC-transplantation into unilateral ischemic limbs was performed in five patients, and both BM-MNC and PB-MNC-transplantation into bilateral ischemic limbs (BM-MNCs into severe ischemic limbs and the same number of PB-MNCs into contralateral less ischemic limbs) were performed in five patients. The number of CD34⁺ cells in PB-MNCs was ~100-fold less than that in BM-MNCs, while PB-MNCs secreted substantial amounts of vascular endothelial growth factor (VEGF) during a 24-hour incubation. There was no increase in the serum VEGF levels by BM-MNC-transplantation alone, while there was a significant increase in the serum VEGF levels after transplantation of both BM-MNCs and PB-MNCs. Two weeks after transplantation, the ankle-brachial index and transcutaneous oxygen pressure were significantly increased in BM-MNC-transplanted limbs, while there were no significant increases in these parameters in PB-MNC-transplanted limbs. In conclusion, autologous transplantation of BM-MNCs represents a new and promising strategy for clinical application designed to revascularize ischemic tissues, but there were no definite therapeutic effects of transplantation of PB-MNCs.