Synergistic effects of autologous cell and hepatocyte growth factor gene therapy for neovascularization in a murine model of hindlimb ischemia

被引：9
作者：
Yamamoto, Yasutaka [1 ]
Matsuura, Takashi [1 ]
Narazaki, Genta [1 ]
Sugitani, Miyoko [1 ]
Tanaka, Kohei [1 ]
Maeda, Akihiro [2 ]
Shiota, Goshi [3 ]
Sato, Kenzo [2 ]
Yoshida, Akio [1 ]
Hisatome, Ichiro [1 ]
机构：
[1] Tottori Univ, Grad Sch Med Sci, Inst Regenerat Med & Biofunct, Div Regenerat Med & Therapeut, Tottori 6838504, Japan
[2] Tottori Univ, Sch Life Sci, Fac Med, Div Mol Biol,Dept Mol & Cellular Biol, Tottori 680, Japan
[3] Tottori Univ, Inst Regenerat Med & Biofunct, Grad Sch Med Sci, Div Mol & Genet Med, Tottori 680, Japan
来源：
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2009年 / 297卷 / 04期
关键词：
angiogenesis; apoptosis; PERIPHERAL ARTERIAL-DISEASE; ACUTE MYOCARDIAL-INFARCTION; LIMB ISCHEMIA; PROGENITOR CELLS; DOUBLE-BLIND; ANGIOGENESIS; TRANSPLANTATION; REGENERATION; EXPRESSION; TRIAL;
D O I：
10.1152/ajpheart.00321.2009
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Yamamoto Y, Matsuura T, Narazaki G, Sugitani M, Tanaka K, Maeda A, Shiota G, Sato K, Yoshida A, Hisatome I. Synergistic effects of autologous cell and hepatocyte growth factor gene therapy for neovascularization in a murine model of hindlimb ischemia. Am J Physiol Heart Circ Physiol 297: H1329-H1336, 2009. First published August 7, 2009; doi: 10.1152/ajpheart.00321.2009.-Autologous cell implantation and angiogenic gene therapy have been evaluated in critical limb ischemic patients. Here, we compared the features of these strategies individually and in combination. C57BL/6J mice with ischemic hindlimbs were injected with adherent mononuclear cells (aMNCs) from bone marrow or adenovirus encoding the hepatocyte growth factor (HGF) gene (Ad-HGF). Under comparable angiogenic conditions, 10 x 10(5) aMNCs produced significantly higher amounts of VEGF and FGF-2 and stimulated the number of arterioles in ischemic muscle compared with 1 x 10(8) plaque-forming units (pfu) of Ad-HGF. Ad-HGF produced 10 times more HGF in ischemic muscle compared with aMNCs. Injection of 0.3 x 10(5) aMNCs previously transfected with Ad-HGF (aMNC/Ad-HGF) increased blood flow and elevated the numbers of capillaries and arterioles to levels comparable with that seen with 10 x 10(5) aMNCs or 1 x 10(8) pfu of Ad-HGF. Hypoxic conditions induced the apoptotic death of aMNCs. However, coincubation with HGF or aMNC/Ad-HGF protected cells against apoptosis. HGF stimulated the migration of aMNCs, and the migration capacity of the aMNC/Ad-HGF group was significantly higher than that in the aMNC/Ad-LacZ group. In conclusion, cell-based HGF gene therapy decreased the number of cells required for neovascularization. This strategy can be an effective angiogenic therapy.
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收藏
页码：H1329 / H1336
页数：8
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