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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Autor principal: Olaiz, N.
Otros Autores: Signori, E., Maglietti, F., Soba, Alejandro, Suárez, C., Turjanski, P., Michinski, S., Marshall, Guillermo Ricardo
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Elsevier 2014
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100 1 |a Olaiz, N. 
245 1 0 |a Tissue damage modeling in gene electrotransfer: The role of pH 
260 |b Elsevier  |c 2014 
270 1 0 |m Marshall, G.; Laboratorio de Sistemas Complejos, Departamento de Computación, FCEyN, Universidad de Buenos AiresArgentina 
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506 |2 openaire  |e Política editorial 
520 3 |a 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.  |l eng 
536 |a Detalles de la financiación: TD1104 
536 |a Detalles de la financiación: Universidad de Buenos Aires, UBACyT X132/08 
536 |a Detalles de la financiación: Ministerio de Ciencia, Tecnología e Innovación Productiva, SLO-AR 08/02/09 
536 |a Detalles de la financiación: Consejo Nacional de Investigaciones Científicas y Técnicas, PIP 112-200801-01087/09 
536 |a Detalles de la financiación: E. Signori is grateful and thanks Prof DJ Wells. F. Maglietti and S. Michinski have scholarships from Consejo Nacional de Investigaciones Cientí ficas y Técnicas (CONICET) and Instituto Tecnológico Buenos Aires (ITBA), respectively. P. Turjanski, N. Olaiz, C. Suárez, A. Soba and G. Marshall are members from CONICET. This work was supported by grants from Universidad de Buenos Aires ( UBACyT X132/08 ), CONICET ( PIP 112-200801-01087/09 ), MINCyT ( SLO-AR 08/02/09 ), ITBACyT 2012 (modalidad I, Nro 1) and Biomedicine and Molecular Biosciences COST Action TD1104 . 
593 |a Laboratorio de Sistemas Complejos, Departamento de Computación, FCEyN, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina 
593 |a Laboratory of Molecular Pathology and Experimental Oncology, CNR-IFT, Rome, Italy 
593 |a Instituto Tecnológico de Buenos Aires, Argentina 
650 1 7 |2 spines  |a PH 
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690 1 0 |a COMPUTATIONAL MODELING 
690 1 0 |a GENE ELECTROTRANSFER 
690 1 0 |a HYALURONIDASE 
690 1 0 |a COMPUTATIONAL MODEL 
690 1 0 |a ELECTROTRANSFER 
690 1 0 |a HYALURONIDASE 
690 1 0 |a TISSUE DAMAGE 
690 1 0 |a HYALURONIDASE 
690 1 0 |a HYALURONOGLUCOSAMINIDASE 
690 1 0 |a ANIMAL EXPERIMENT 
690 1 0 |a ANIMAL MODEL 
690 1 0 |a ANIMAL TISSUE 
690 1 0 |a ARTICLE 
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690 1 0 |a CONTROLLED STUDY 
690 1 0 |a ELECTRIC CURRENT 
690 1 0 |a ELECTRODE 
690 1 0 |a ELECTROPORATION 
690 1 0 |a FEMALE 
690 1 0 |a GENE TARGETING 
690 1 0 |a ION TRANSPORT 
690 1 0 |a MATHEMATICAL MODEL 
690 1 0 |a MICROSCOPY 
690 1 0 |a MOUSE 
690 1 0 |a MUSCLE INJURY 
690 1 0 |a NONHUMAN 
690 1 0 |a SKELETAL MUSCLE 
690 1 0 |a SKINFOLD 
690 1 0 |a TIBIALIS ANTERIOR MUSCLE 
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690 1 0 |a MALE 
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690 1 0 |a CATTLE 
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690 1 0 |a GENE TRANSFER TECHNIQUES 
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690 1 0 |a HYDROGEN-ION CONCENTRATION 
690 1 0 |a MALE 
690 1 0 |a MICE 
690 1 0 |a MODELS, BIOLOGICAL 
690 1 0 |a MUSCLE, SKELETAL 
700 1 |a Signori, E. 
700 1 |a Maglietti, F. 
700 1 |a Soba, Alejandro 
700 1 |a Suárez, C. 
700 1 |a Turjanski, P. 
700 1 |a Michinski, S. 
700 1 |a Marshall, Guillermo Ricardo 
773 0 |d Elsevier, 2014  |g v. 100  |h pp. 105-111  |p Bioelectrochemistry  |x 15675394  |w (AR-BaUEN)CENRE-3947  |t Bioelectrochemistry 
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