Enhancement of Angiogenic Efficacy of Human Cord Blood Cell Transplantation

We tested the hypotheses that angiogenic efficacy of cord blood mononuclear cell (CBMNC) transplantation would be enhanced by using matrix and that combined therapy of CBMNC transplantation using matrix and sustained delivery of basic fibroblast growth factor (bFGF) would be synergistic in angiogenesis induction in ischemic limbs. One day after surgical induction of hindlimb ischemia, C57BL/6J mice were randomized to receive either medium injection, CBMNC transplantation using medium, CBMNC transplantation using fibrin matrix, sustained delivery of bFGF, or a combination of sustained delivery of bFGF and CBMNC transplantation using fibrin matrix. Four weeks after treatment, the angiogenic efficacy of the treatments was evaluated by immunohistochemical examinations and microvessel density determination in the ischemic sites. Transplanted CBMNCs survived, proliferated, and participated in capillary formation in ischemic limbs. CBMNC transplantation using fibrin matrix significantly increased the densities of capillaries and arterioles compared with CBMNC transplantation using medium. Importantly, combined therapy of sustained delivery of bFGF and CBMNC transplantation using fibrin matrix further increased the densities of capillaries and arterioles compared with either therapy alone. The angiogenic efficacy of angiogenic cell transplantation is enhanced by cell transplantation using matrix. Combined therapy of sustained release of angiogenic protein and angiogenic cell transplantation synergistically enhances angiogenesis in ischemic limbs compared to each therapy separately.