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Articles in PresS, published online ahead of print September 19, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00547.2002
Submitted on July 1, 2002
Accepted on September 3, 2002
1 Division of Cardiovascular Surgery, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
2 Division of Critical Care Medicine, Department of Medical Bioregulation, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
3 Division of Emergency and Critical Care Medicine, Department of Stress and Bio-response Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
* To whom correspondence should be addressed. E-mail: kimikazu{at}yamaguchi-u.ac.jp.
The angiogenic effect induced by autologous bone marrow cell implantation (BMCI) was examined in the ischemic hindlimbs of diabetic and non-diabetic 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 x 107 bone marrow cells were injected intramuscularly at six points, into the ischemic limbs and regional perfusion recovery was evaluated by colored microspheres 2 weeks later. No difference was found in the release of angiogenic factors or endothelial differentiation from bone marrow cells in vitro between the diabetic and non-diabetic rats. The levels of nitric oxide (NO) in plasma were significantly lower, and native perfusion recovery in the ischemic hindlimbs was significantly slower in the diabetic rats than in the non-diabetic rats. However, while perfusion recovery was achieved in the ischemic hindlimbs, there was no significant increase in systemic VEGF after BMCI treatment in either the diabetic or non-diabetic rats. Therefore, therapeutic angiogenesis induced by BMCI could be a safe and effective treatment for ischemic limb disease in diabetic patients.
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