Tissue damage modeling in gene electrotransfer: The role of pH

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...

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Autores principales:	Soba, Alejandro, Suárez, Cecilia Ana, Turjanski, Pablo Guillermo
Publicado:	2014
Materias:	Computational modeling Gene electrotransfer Hyaluronidase PH Computational model Electrotransfer Tissue damage pH hyaluronidase hyaluronoglucosaminidase animal experiment animal model animal tissue Article computer model controlled study electric current electrode electroporation female gene targeting ion transport mathematical model microscopy mouse muscle injury nonhuman skeletal muscle skinfold tibialis anterior muscle tissue injury tissue necrosis adverse effects animal biological model bovine drug effects gene transfer male metabolism Animals Cattle Electroporation Gene Transfer Techniques Hyaluronoglucosaminidase Hydrogen-Ion Concentration Male Mice Models, Biological Muscle, Skeletal
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15675394_v100_n_p105_Olaiz http://hdl.handle.net/20.500.12110/paper_15675394_v100_n_p105_Olaiz
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_15675394_v100_n_p105_Olaiz
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spelling	paper:paper_15675394_v100_n_p105_Olaiz2023-06-08T16:24:04Z Tissue damage modeling in gene electrotransfer: The role of pH Soba, Alejandro Suárez, Cecilia Ana Turjanski, Pablo Guillermo Computational modeling Gene electrotransfer Hyaluronidase PH Computational model Electrotransfer Hyaluronidase Tissue damage pH hyaluronidase hyaluronoglucosaminidase animal experiment animal model animal tissue Article computer model controlled study electric current electrode electroporation female gene targeting ion transport mathematical model microscopy mouse muscle injury nonhuman pH skeletal muscle skinfold tibialis anterior muscle tissue injury tissue necrosis adverse effects animal biological model bovine drug effects gene transfer male metabolism pH Animals Cattle Electroporation Gene Transfer Techniques Hyaluronoglucosaminidase Hydrogen-Ion Concentration Male Mice Models, Biological Muscle, Skeletal 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 183. V/cm in a GET protocol and 158. V/cm in a hyaluronidase + GET protocol. © 2014 Elsevier B.V. Fil:Soba, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Suárez, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Turjanski, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15675394_v100_n_p105_Olaiz http://hdl.handle.net/20.500.12110/paper_15675394_v100_n_p105_Olaiz
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Computational modeling Gene electrotransfer Hyaluronidase PH Computational model Electrotransfer Hyaluronidase Tissue damage pH hyaluronidase hyaluronoglucosaminidase animal experiment animal model animal tissue Article computer model controlled study electric current electrode electroporation female gene targeting ion transport mathematical model microscopy mouse muscle injury nonhuman pH skeletal muscle skinfold tibialis anterior muscle tissue injury tissue necrosis adverse effects animal biological model bovine drug effects gene transfer male metabolism pH Animals Cattle Electroporation Gene Transfer Techniques Hyaluronoglucosaminidase Hydrogen-Ion Concentration Male Mice Models, Biological Muscle, Skeletal
spellingShingle	Computational modeling Gene electrotransfer Hyaluronidase PH Computational model Electrotransfer Hyaluronidase Tissue damage pH hyaluronidase hyaluronoglucosaminidase animal experiment animal model animal tissue Article computer model controlled study electric current electrode electroporation female gene targeting ion transport mathematical model microscopy mouse muscle injury nonhuman pH skeletal muscle skinfold tibialis anterior muscle tissue injury tissue necrosis adverse effects animal biological model bovine drug effects gene transfer male metabolism pH Animals Cattle Electroporation Gene Transfer Techniques Hyaluronoglucosaminidase Hydrogen-Ion Concentration Male Mice Models, Biological Muscle, Skeletal Soba, Alejandro Suárez, Cecilia Ana Turjanski, Pablo Guillermo Tissue damage modeling in gene electrotransfer: The role of pH
topic_facet	Computational modeling Gene electrotransfer Hyaluronidase PH Computational model Electrotransfer Hyaluronidase Tissue damage pH hyaluronidase hyaluronoglucosaminidase animal experiment animal model animal tissue Article computer model controlled study electric current electrode electroporation female gene targeting ion transport mathematical model microscopy mouse muscle injury nonhuman pH skeletal muscle skinfold tibialis anterior muscle tissue injury tissue necrosis adverse effects animal biological model bovine drug effects gene transfer male metabolism pH Animals Cattle Electroporation Gene Transfer Techniques Hyaluronoglucosaminidase Hydrogen-Ion Concentration Male Mice Models, Biological Muscle, Skeletal
description	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 183. V/cm in a GET protocol and 158. V/cm in a hyaluronidase + GET protocol. © 2014 Elsevier B.V.
author	Soba, Alejandro Suárez, Cecilia Ana Turjanski, Pablo Guillermo
author_facet	Soba, Alejandro Suárez, Cecilia Ana Turjanski, Pablo Guillermo
author_sort	Soba, Alejandro
title	Tissue damage modeling in gene electrotransfer: The role of pH
title_short	Tissue damage modeling in gene electrotransfer: The role of pH
title_full	Tissue damage modeling in gene electrotransfer: The role of pH
title_fullStr	Tissue damage modeling in gene electrotransfer: The role of pH
title_full_unstemmed	Tissue damage modeling in gene electrotransfer: The role of pH
title_sort	tissue damage modeling in gene electrotransfer: the role of ph
publishDate	2014
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15675394_v100_n_p105_Olaiz http://hdl.handle.net/20.500.12110/paper_15675394_v100_n_p105_Olaiz
work_keys_str_mv	AT sobaalejandro tissuedamagemodelingingeneelectrotransfertheroleofph AT suarezceciliaana tissuedamagemodelingingeneelectrotransfertheroleofph AT turjanskipabloguillermo tissuedamagemodelingingeneelectrotransfertheroleofph
_version_	1768546741376778240

Tissue damage modeling in gene electrotransfer: The role of pH

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