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Am J Physiol Heart Circ Physiol 284: H66-H70, 2003. First published September 19, 2002; doi:10.1152/ajpheart.00547.2002
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Vol. 284, Issue 1, H66-H70, January 2003

Autologous bone marrow cell implantation as therapeutic angiogenesis for ischemic hindlimb in diabetic rat model

Ken Hirata1, Tao-Sheng Li1, Masahiko Nishida1, Hiroshi Ito1, Masunori Matsuzaki2, Shunji Kasaoka3, and Kimikazu Hamano1

1 Division of Cardiovascular Surgery and 2 Division of Cardiovascular Medicine, Department of Medical Bioregulation, and 3 Division of Emergency and Critical Care Medicine, Department of Stress and Bio-response Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan

The angiogenic effect induced by autologous bone marrow cell implantation (BMCI) was examined in the ischemic hindlimbs of diabetic and nondiabetic rats. Diabetes mellitus was induced by the systemic administration of streptozotocin. We investigated the production of angiogenic factors and endothelial differentiation from bone marrow cells and the native recovery of blood flow in the ischemic hindlimbs. To observe the angiogenic effect induced by BMCI treatment, 6 × 107 bone marrow cells were injected intramuscularly at six points into the ischemic limbs, and regional perfusion recovery was evaluated with colored microspheres 2 wk later. No difference was found between diabetic and nondiabetic rats in the release of angiogenic factors or endothelial differentiation from bone marrow cells in vitro. The levels of nitric oxide in plasma were significantly lower, and native perfusion recovery in the ischemic hindlimbs was significantly slower in the diabetic rats than in the nondiabetic rats. However, although perfusion recovery was achieved in the ischemic hindlimbs, there was no significant increase in systemic VEGF after BMCI treatment in either the diabetic or nondiabetic rats. Therefore, therapeutic angiogenesis induced by BMCI could be a safe and effective treatment for ischemic limb disease in diabetic patients.

diabetes mellitus; angiogenic factor; endothelial differentiation; colored microsphere


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