title: Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model.
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.
authors.affiliation: Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: D
authors.initials: D
authors.lastname: Ladage
authors.forename: I C
authors.initials: IC
authors.lastname: Turnbull
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Takewa
authors.forename: K
authors.initials: K
authors.lastname: Rapti
authors.forename: C
authors.initials: C
authors.lastname: Morel
authors.forename: I
authors.initials: I
authors.lastname: Karakikes
authors.forename: L
authors.initials: L
authors.lastname: Hadri
authors.forename: J
authors.initials: J
authors.lastname: Müller-Ehmsen
authors.forename: K D
authors.initials: KD
authors.lastname: Costa
authors.forename: R J
authors.initials: RJ
authors.lastname: Hajjar
authors.forename: Y
authors.initials: Y
authors.lastname: Kawase
mesh_terms: D000256:Adenoviridae; D000279:Administration, Cutaneous; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D016503:Drug Delivery Systems / Q000379:methods*; D005455:Fluorescent Antibody Technique; D005471:Fluoroscopy; D005781:Gelatin Sponge, Absorbable / Q000008:administration & dosage*; D005822:Genetic Vectors / Q000008:administration & dosage*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009203:Myocardial Infarction / Q000188:drug therapy*; D010496:Pericardium / Q000000981:diagnostic imaging*; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D018084:Ultrasonography, Interventional
chemical_list: D017931:DNA Primers; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins