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Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation

Gene Therapy volume 17, pages 763–769 (2010)Cite this article

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Abstract

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.

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Acknowledgements

We thank William Marshall, MD (University of South Florida, College of Medicine) for his insight into vascular biology and valuable review of the article and Mark Jaroszeski (University of South Florida, College of Engineering) for construction of the MultiElectrode Array. This work was supported by the Defense Threat Reduction Agency and the Florida Center of Excellence for Biomolecular Identification and Targeted Therapeutics.

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Authors and Affiliations

  1. Department of Molecular Medicine, University of South Florida, Tampa, FL, USA

    B Ferraro, Y L Cruz & R Heller

  2. Division of Comparative Medicine, University of South Florida, Tampa, FL, USA

    M Baldwin

  3. Department of Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    D Coppola

  4. Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA, USA

    R Heller

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  1. B Ferraro
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Correspondence to R Heller.

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Competing interests

Richard Heller is an inventor on patents used in this work. These patents have been licensed to RMR Technologies, LLC and Inovio Biomedical Corporation. Richard Heller has ownership interest in RMR Technologies and owns stock and stock options of Inovio Biomedical Corporation.

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Ferraro, B., Cruz, Y., Baldwin, M. et al. Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation. Gene Ther 17, 763–769 (2010). https://doi.org/10.1038/gt.2010.43

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