Less Invasive Gene Therapy using Macrophages for Ischemic Heart Disease Hisanori Fujikura 1 , Naoto Fukuyama 2,4 , Etsuro Tanaka 2,4 , Miyoko Yoshida 2 , Eriko Kuwabara 3 , Koji Kimura 3 , Takako Goto 3 , Takashi Hayashi 3 , Johbu Itoh 5 , Yoshiro Shinozaki 2 , Yasuhiko Tabata 6 , Shunnosuke Handa 1 , Hidezo Mori 7 1Department of Cardiology, Tokai University School of Medicine 2Department of Physiology, Tokai University School of Medicine 3Department of Cardiovascular Surgery, Tokai University School of Medicine 4Department of Center for Regenerative Medicine, Tokai University School of Medicine 5Department of Laboratories for Structure and Function Research, Tokai University School of Medicine 6Institute for Frontier Medical Sciences, Kyoto University 7Department of Cardiac Physiology, National Cardiovascular Center Research Institute Keyword: 遺伝子発現 , マクロファージ , 心筋梗塞 , gene expression , macrophages , myocardial infarction pp.1157-1161
Published Date 2002/11/15
DOI https://doi.org/10.11477/mf.1404902568
  • Abstract
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 We have developed a new gene-targeting method using macrophages. Positively charged lattice structures of gelatin combine with negatively charged DNA. We aimed at targeting genes towards jeopardized myocardial tissue using macrophages which had been transfected with gelatin-DNA complex and had been introduced into the peripheral vein. The gelatin was impregnated with DNA-encoding green fluorescent protein (GFP). The GFP-gene was transfected into rat peritoneal macrophages by means of co-culturing with gelatin-GFP gene complex over a period of 14 days. Anesthetized rats were subjected to 180 minutes of ligation of the left anterior descending coronary artery. and the transfected macrophages were injected into the superficial dorsal vein of the penis, followed by 60 minutes of reperfusion. The heart was removed, and extrinsic macrophages were analyzed with light microscopy. GFP expression was confirmed in 30.2±5.1% of macrophages as evidenced by FACS analysis. Immunohistochemical analyses revealed that GFP-antigen-positive cells existed in the jeopardized myocardium rather than in normal regions. Thus, macrophages transfected by gelatin-DNA complex administered through a peripheral vein were able to target jeopardized myocardial tissue in rats. The present system has advantages in that there is less invasiveness, a higher transfection rate, and more tissue targeting ability.

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