期刊
GENE THERAPY
卷 18, 期 10, 页码 979-985出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2011.52
关键词
pericardium; adenovirus; mesenchymal stem cells; gelfoam
类别
资金
- National Institutes of Health [R01HL078731, R01HL080498, R01HL083156, R01HL093183, R01HL088434, P20HL100396, R21HL095980]
- Transatlantic Leducq Foundation
- National Heart, Lung, and Blood Institute, National Institutes of Health [HHSN268201000045C]
- German Research Foundation (DFG)
Intrapericardial drug delivery is a promising procedure, with the ability to localize therapeutics with the heart. Gelfoam particles are nontoxic, inexpensive, nonimmunogenic and biodegradable compounds that can be used to deliver therapeutic agents. We developed a new percutaneous approach method for intrapericardial injection, puncturing the pericardial sac safely under fluoroscopy and intravascular ultrasound (IVUS) guidance. In a porcine model of myocardial infarction (MI), we deployed gelfoam particles carrying either (a) autologous mesenchymal stem cells (MSCs) or (b) an adenovirus encoding enhanced green fluorescent protein (eGFP) 48 h post-MI. The presence of MSCs and viral infection at the infarct zone was confirmed by immunoflourescence and PCR. Puncture was performed successfully in 16 animals. Using IVUS, we successfully determined the size of the pericardial space before the puncture, and safely accessed that space in setting of pericardial effusion and also adhesions induced by the MI. Intrapericardial injection of gelfoam was safe and reliable. Presence of the MSCs and eGFP expression from adenovirus in the myocardium were confirmed after delivery. Our novel percutaneous approach to deliver (stem-) cells or adenovirus was safe and efficient in this pre-clinical model. IVUS-guided delivery is a minimally invasive procedure that seems to be a promising new strategy to deliver therapeutic agents locally to the heart. Gene Therapy (2011) 18, 979-985; doi:10.1038/gt.2011.52; published online 21 April 2011
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