Document Detail


Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation.
MedLine Citation:
PMID:  20393507     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gene therapy approaches delivering fibroblast growth factor-2 (FGF-2) have shown promise as a potential treatment for increasing blood flow to ischemic limbs. Currently, effective noninvasive techniques to deliver plasmids encoding genes of therapeutic interest, such as FGF-2, are limited. We sought to determine if intradermal injection of plasmid DNA encoding FGF-2 (pFGF) followed by noninvasive cutaneous electroporation (pFGFE+) could increase blood flow and angiogenesis in a rat model of hindlimb ischemia. pFGFE+ or control treatments were administered on postoperative day 0. Compared to injection of pFGF alone (pFGFE-), delivery of pFGFE+ significantly increased FGF-2 expression for 10 days. Further, the increase in FGF-2 expression with pFGFE+ was sufficient to significantly increase ischemic limb blood flow, measured by laser Doppler perfusion imaging, beginning on postoperative day 3. Ischemic limb blood flow in the pFGFE+ treatment group remained significantly higher than all control groups through the end point of the study, postoperative day 14. Immunohistochemical staining of gastrocnemius cross sections determined there was a twofold increase in capillary density in the pFGFE+ treatment group. Our results suggest that pFGFE+ is a potential noninvasive, nonviral therapeutic approach to increase perfusion and angiogenesis for the treatment of limb ischemia.
Authors:
B Ferraro; Y L Cruz; M Baldwin; D Coppola; R Heller
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-04-15
Journal Detail:
Title:  Gene therapy     Volume:  17     ISSN:  1476-5462     ISO Abbreviation:  Gene Ther.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-10     Completed Date:  2010-09-27     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  763-9     Citation Subset:  IM    
Affiliation:
Department of Molecular Medicine, University of South Florida, Tampa, FL, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Electroporation
Fibroblast Growth Factor 2 / biosynthesis,  genetics*
Gene Therapy / methods*
Gene Transfer Techniques
Hindlimb / blood supply*
Ischemia / therapy*
Neovascularization, Physiologic
Peripheral Vascular Diseases / therapy
Rats
Regional Blood Flow
Grant Support
ID/Acronym/Agency:
R01 EB005441-03/EB/NIBIB NIH HHS; R01 EB005441-04/EB/NIBIB NIH HHS; R01 EB005441-05/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
103107-01-3/Fibroblast Growth Factor 2
Comments/Corrections
Comment In:
Gene Ther. 2010 Jun;17(6):691   [PMID:  20463758 ]

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