Autologous bone marrow cell implantation as therapeutic angiogenesis for ischemic hindlimb in diabetic rat model.
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 x 10(7) 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.
Hirata
Ken
K
Division of Cardiovascular Surgery, Department of Medical Bioregulation, Yamaguchi University School of Medicine, Ube, Japan.
Li
Tao-Sheng
TS
Nishida
Masahiko
M
Ito
Hiroshi
H
Matsuzaki
Masunori
M
Kasaoka
Shunji
S
Hamano
Kimikazu
K
D000818:Animals; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental; D003925:Diabetic Angiopathies / Q000503:physiopathology / Q000601:surgery*; D015536:Down-Regulation; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D006614:Hindlimb / Q000098:blood supply* / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007511:Ischemia / Q000503:physiopathology / Q000601:surgery*; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow; D014182:Transplantation, Autologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide