期刊论文详细信息
BMC Biotechnology
A visible, targeted high-efficiency gene delivery and transfection strategy
Qiao-Ying Yuan2  Jing Huang3  Bao-Cheng Chu1  Xing-Sheng Li3  Liang-Yi Si2 
[1] BioMolecular Imaging Center, Department of Radiology, University of Washington, Seattle, WA 98109, USA
[2] Department of Geriatrics, Southwest Hospital, the Third Military Medical University, Chongqing 400038, China
[3] Institute of Ultrasound Imaging, The Chongqing University of Medical Sciences, Chongqing 400010, China
关键词: angiogenesis;    gene expression;    microbubbles;    angiogenic gene;    Intramyocardial delivery;   
Others  :  1146186
DOI  :  10.1186/1472-6750-11-56
 received in 2010-12-11, accepted in 2011-05-21,  发布年份 2011
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【 摘 要 】

Background

To enhance myocardial angiogenic gene expression, a novel gene delivery strategy was tested. Direct intramyocardial injection of an angiogenic gene with microbubbles and insonation were applied in a dog animal model. Dogs received one of the four different treatments in conjunction with either the enhanced green fluorescence protein (EGFP) gene or the hepatocyte growth factor (HGF) gene: gene with microbubbles (MB) and ultrasound (US); gene with US; gene with MB; or the gene alone.

Results

Distribution of MB and the gene in the myocardium was visualized during the experiment. Compared with the EGFP gene group, an average 14.7-fold enhancement in gene expression was achieved in the EGFP+MB/US group (P < 0.01). Compared with the HGF gene group, an average 10.7-fold enhancement in gene expression was achieved in the HGF+MB/US group (P < 0.01). In addition, capillary density increased from 20.8 ± 3.4/mm2 in the HGF gene group to 146.7 ± 31.4/mm2 in HGF+MB/US group (P < 0.01).

Conclusions

Thus, direct intramyocardial injection of an angiogenic gene in conjunction with microbubbles plus insonation synergistically enhances angiogenesis. This method offers an observable gene delivery procedure with enhanced expression efficiency of the delivered gene.

【 授权许可】

   
2011 Yuan et al; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Losordo DW, Vale PR, Symes JF, Dunnington CH, Esakof DD, Maysky M, Ashare AB, Lathi K, Isner JM: Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF-165 as sole therapy for myocardial ischemia. Circulation 1998, 98:2800-2804.
  • [2]Choi D, Hwang KC, Lee KY, Kim YH: Ischemic heart diseases: Current treatments and future. J Control Release 2009, 140:194-202.
  • [3]Chen XH, Minatoguchi S, Kosai K, Yuge K, Takahashi T, Arai M, Wang N, Misao Y, Lu C, Onogi H, Kobayashi H, Yasuda S, Ezaki M, Ushikoshi H, Takemura G, Fujiwara T, Fujiwara H: In vivo hepatocyte growth factor gene transfer reduces myocardial ischemia-reperfusion injury through its multiple actions. J Card Fail 2007, 13:874-883.
  • [4]Azuma J, Taniyama Y, Takeya Y, Iekushi K, Aoki M, Dosaka N, Matsumoto K, Nakamura T, Ogihara T, Morishita R: Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac dysfunction in porcine ischemic cardiomyopathy. Gene Ther 2006, 13:1206-1213.
  • [5]Gupta R, Tongers J, Losordo DW: Human Studies of Angiogenic Gene Therapy. Circ Res 2009, 105:724-736.
  • [6]Li Y, Takemura G, Kosai K, Yuge K, Nagano S, Esaki M, Goto K, Takahashi T, Hayakawa K, Koda M, Kawase Y, Maruyama R, Okada H, Minatoguchi S, Mizuguchi H, Fujiwara T, Fujiwara H: Postinfarction treatment with an adenoviral vector expressing hepatocyte growth factor relieves chronic left ventricular remodeling and dysfunction in mice. Circulation 2003, 107:2499-2506.
  • [7]Krombach GA, Pfeffer JG, Kinzel S, Katoh M, Günther RW, Buecker A: MR-guided Percutaneous Intramyocardial Injection with an MR-compatible Catheter: Feasibility and Changes in T1 Values after Injection of Extracellular Contrast Medium in Pigs. Radiology 2005, 235:487-494.
  • [8]Eshet DM, Adam D, Machluf M: The effects of albumin-coated microbubbles in DNA delivery mediated by therapeutic ultrasound. J Control Release 2006, 112:156-166.
  • [9]Cohen T, Juang G: Utility of intracardiac echocardiography to facilitate transvenous coronary sinus lead placement for biventricular cardioverter-defibrillator implantation. J Invas Cardiol 2003, 15:685-686.
  • [10]Bekeredjian A, Grayburn PA, Shohet RV: Use of Ultrasound Contrast Agents for Gene or Drug Delivery in Cardiovascular Medicine. J Am Coll Cardiol 2005, 45:329-335.
  • [11]Isao K, Koji O, Akira O, Hiroto T: Treatment of Acute Myocardial Infarction by Hepatocyte Growth Factor Gene Transfer: The First Demonstration of Myocardial Transfer of a "Functional" Gene Using Ultrasonic Microbubble Destruction. J Am Coll Cardiol 2004, 44:644-653.
  • [12]Li X, Wang Z, Ran H, Li X, Yuan Q, Zheng Y, Ren J, Su L, Zhang W, Li Q, Xu C: Experimental research on therapeutic angiogenesis induced by hepatocyte growth factor directed by ultrasound-targeted microbubble destruction in rats. J Ultras Med 2008, 27:453-460.
  • [13]Shohet RV, Chen S, Zhou YT, Wang Z, Meidell RS, Unger RH, Grayburn PA: Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 2000, 101:2554-2556.
  • [14]Skyba DM, Price RJ, Linka AZ, Skalak TC, Kaul S: Direct in vivo visualization of intravascular destruction of microbubbles by ultrasound and its local effects on tissue. Circulation 1998, 98:290-293.
  • [15]Jeane MT, Feng X: Richard Thomas Porter The use of microbubbles to target drug delivery. Cardiovascular Ultrasound 2004, 2:23. BioMed Central Full Text
  • [16]Hwang M, Niermann KL, Andrej F, Arthur C: Sonographic Assessment of Tumor Response: From In Vivo Models to Clinical. Applications Ultrasound Quarterly 2009, 25:175-183.
  • [17]Bekeredjian R, Kroll RD, Fein E, Tinkov S, Coester C, Winter G, Katus HA, Kulaksiz H: Ultrasound targeted microbubble destruction increases capillary permeability in hepatomas. Ultrasound Med Biol 2007, 33:1592-1598.
  • [18]Mark RS, Jason O, William PH: Green fluorescent protein is a quantitative reporter of gene expression in individual eukaryotic cells. The FASEB Journal 2005, 19:440-442.
  • [19]Li TL, Tachibana K, Motomu K, Masahide K: Gene Transfer with Echo-enhanced Contrast Agents: Comparison between Albunex, Optison, and Levovist in Mice--Initial Results. Radiology 2003, 229:423-428.
  • [20]Bodh IJ, Vijayan M, Dinender K, Halliday I: Vascular remodeling during healing after myocardial infarction in the dog model: Effects of reperfusion, amlodipine and enalapril. J Am Coll Cardiol 2002, 39:1538-1545.
  • [21]Nicholas JF, Shigekoto K, Lewis CB, Bertram P: Regional myocardial blood flow in the dog studied with radioactive microspheres. Cardiovasc Res 1971, 5:331-336.
  • [22]Isner JM: Myocardial gene therapy. Nature 2002, 415:234-239.
  • [23]Kwon JS, Park IK, Cho AS, Shin SM, Hong MH, Jeong SY, Kim YS, Min JJ, Jeong MH, Kim WJ, Jo S, Pun SH, Cho JG, Park JC, Kang JC, Ahn Y: Enhanced angiogenesis mediated by vascular endothelial growth factor plasmid-loaded thermo-responsive amphiphilic polymer in a rat myocardial infarction model. J Control Release 2009, 138:168-176.
  • [24]Markkanen JE, Rissanen TT, Kivelä A, Ylä-Herttuala S: Growth factor-induced therapeutic angiogenesis and arteriogenesis in the heart--gene therapy. Cardiovasc Res 2005, 65:656-664.
  • [25]Shohet RV, Chen S, Zhou YT: Echocardiographic destruction of albumin microbubbles directs gene delivery to the myocardium. Circulation 2000, 101:2554-2556.
  • [26]Beeri R, Guerrero JL, Supple G, Sullivan S, Levine RA, Hajjar RJ: New efficient catheter-based system for myocardial gene delivery. Circulation 2002, 106:1756-1759.
  • [27]Taniyama Y, Tachibana K, Hiraoka K, Aoki M, Yamamoto S, Matsumoto K, Nakamura T, Ogihara T, Kaneda Y, Morishita R: Development of safe and efficient novel nonviral gene transfer using ultrasound: enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle. Gene Ther 2002, 9:372-380.
  • [28]Bekeredjian R, Chen SY, Peter AF, Grayburn PA, Shohet RV: Ultrasound-targeted microbubble destruction can repeatedly direct highly specific plasmid expression to the heart. Circulation 2003, 108:1022-1026.
  • [29]Kawabata K, Takakura Y, Hashida M: The fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake. Pharm Res 1995, 12:825-830.
  • [30]Miyake Y, Ohmori K, Yoshida J, Ishizawa M, Mizukawa M, Yukiiri K, Kohno M: Granulocyte colony-stimulating factor facilitates the angiogenesis induced by ultrasonic microbubble destruction. Ultrasound Med Biol 2007, 33:1796-1804.
  • [31]Chappell JC, Song J, Klibanov AL, Price RJ: Ultrasonic microbubble destruction stimulates therapeutic arteriogenesis via the CD18-dependent recruitment of bone marrow-derived cells. Arterioscl Throm Vas 2008, 28:1117-1122.
  • [32]Schwarz ER, Speakman MT, Patterson M, Hale SS, Isner JM, Kedes LH, Kloner RA: Evaluation of the effects of intramyocardial injection of DNA expressing vascular endothelial growth factor (VEGF) in a myocardial infarction model in the rat--angiogenesis and angioma formation. J Am Coll Cardiol 2000, 35:1323-1330.
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