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Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model

Gene Therapy volume 18, pages 979–985 (2011)Cite this article

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Abstract

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.

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Acknowledgements

We thank James Lough and Catherine McMahon for their excellent technical assistance. This work was supported by grants from the National Institutes of Health: R01HL078731, R01HL080498, R01HL083156, R01HL093183, R01HL088434 and P20HL100396 (RJH) and R21HL095980 (KDC), from the Transatlantic Leducq Foundation (RJH) and the National Heart, Lung, and Blood Institute, National Institutes of Health, as a Program of Excellence in Nanotechnology (PEN) Award, Contract #HHSN268201000045C. DL was supported by the German Research Foundation (DFG).

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Authors and Affiliations

  1. Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA

    D Ladage, I C Turnbull, K Ishikawa, Y Takewa, K Rapti, C Morel, I Karakikes, L Hadri, K D Costa, R J Hajjar & Y Kawase

  2. Department III for Internal Medicine, University of Cologne, Cologne, Germany

    J Müller-Ehmsen

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  1. D Ladage
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Correspondence to Y Kawase.

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Ladage, D., Turnbull, I., Ishikawa, K. et al. Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model. Gene Ther 18, 979–985 (2011). https://doi.org/10.1038/gt.2011.52

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