Document Detail


Delivery of gelfoam-enabled cells and vectors into the pericardial space using a percutaneous approach in a porcine model.
MedLine Citation:
PMID:  21512506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
D Ladage; I C Turnbull; K Ishikawa; Y Takewa; K Rapti; C Morel; I Karakikes; L Hadri; J Müller-Ehmsen; K D Costa; R J Hajjar; Y Kawase
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-21
Journal Detail:
Title:  Gene therapy     Volume:  18     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-13     Completed Date:  2012-01-30     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  979-85     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae
Administration, Cutaneous
Animals
DNA Primers / genetics
Drug Delivery Systems / methods*
Fluorescent Antibody Technique
Fluoroscopy
Gelatin Sponge, Absorbable / administration & dosage*
Genetic Vectors / administration & dosage*
Green Fluorescent Proteins / metabolism
Immunohistochemistry
Mesenchymal Stem Cell Transplantation / methods*
Myocardial Infarction / drug therapy*
Pericardium / ultrasonography*
Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Swine
Ultrasonography, Interventional
Grant Support
ID/Acronym/Agency:
HHSN268201000045C/HL/NHLBI NIH HHS; HHSN268201000045C//PHS HHS; K01 HL103176/HL/NHLBI NIH HHS; P20 HL100396/HL/NHLBI NIH HHS; P20HL100396/HL/NHLBI NIH HHS; R01 HL083156/HL/NHLBI NIH HHS; R01 HL088434/HL/NHLBI NIH HHS; R01HL078731/HL/NHLBI NIH HHS; R01HL080498/HL/NHLBI NIH HHS; R01HL083156/HL/NHLBI NIH HHS; R01HL088434/HL/NHLBI NIH HHS; R01HL093183/HL/NHLBI NIH HHS; R21HL095980/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/enhanced green fluorescent protein; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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