Document Detail


Tissue damage modeling in gene electrotransfer: The role of pH.
MedLine Citation:
PMID:  24925861     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Optimal gene electrotransfer (GET) requires a compromise between maximum transgene expression and minimal tissue damage. GET in skeletal muscle can be improved by pretreatment with hyaluronidase which contributes to maximize transgene uptake and expression. Nevertheless, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency. Here we analyze the role of pH in tissue damage in GET protocols through in vivo modeling using a transparent chamber implanted into the dorsal skinfold of a mouse (DSC) and intravital microscopy, and in silico modeling using the Poisson-Nernst-Planck equations for ion transport. DSC intravital microscopy reveals the existence of pH fronts emerging from both electrodes and that these fronts are immediate and substantial thus giving rise to tissue necrosis. Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, pH fronts are the principal cause of muscle damage near the electrodes. It also predicts that an optimal efficiency in GET protocols, that is a compromise between obtaining maximum electroporated area and minimal tissue damage, is achieved when the electric field applied is near 183V/cm in a GET protocol and 158V/cm in a hyaluronidase+GET protocol.
Authors:
N Olaiz; E Signori; F Maglietti; A Soba; C Suárez; P Turjanski; S Michinski; G Marshall
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-14
Journal Detail:
Title:  Bioelectrochemistry (Amsterdam, Netherlands)     Volume:  -     ISSN:  1878-562X     ISO Abbreviation:  Bioelectrochemistry     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-6-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100953583     Medline TA:  Bioelectrochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier B.V. All rights reserved.
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