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Olaiz, N.; Signori, E.; Maglietti, F.; Soba, A.; Suárez, C.; Turjanski, P.; Michinski, S.; Marshall, G. "Tissue damage modeling in gene electrotransfer: The role of pH" (2014) Bioelectrochemistry. 100:105-111
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Abstract:

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.

Registro:

Documento: Artículo
Título:Tissue damage modeling in gene electrotransfer: The role of pH
Autor:Olaiz, N.; Signori, E.; Maglietti, F.; Soba, A.; Suárez, C.; Turjanski, P.; Michinski, S.; Marshall, G.
Filiación:Laboratorio de Sistemas Complejos, Departamento de Computación, FCEyN, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Laboratory of Molecular Pathology and Experimental Oncology, CNR-IFT, Rome, Italy
Instituto Tecnológico de Buenos Aires, Argentina
Palabras clave: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
Año:2014
Volumen:100
Página de inicio:105
Página de fin:111
DOI: http://dx.doi.org/10.1016/j.bioelechem.2014.05.001
Título revista:Bioelectrochemistry
Título revista abreviado:Bioelectrochemistry
ISSN:15675394
CODEN:BIOEF
CAS:hyaluronidase, 9001-54-1, 9055-18-9, 488712-31-8; hyaluronoglucosaminidase, 37326-33-3; Hyaluronoglucosaminidase
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15675394_v100_n_p105_Olaiz

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Citas:

---------- APA ----------
Olaiz, N., Signori, E., Maglietti, F., Soba, A., Suárez, C., Turjanski, P., Michinski, S.,..., Marshall, G. (2014) . Tissue damage modeling in gene electrotransfer: The role of pH. Bioelectrochemistry, 100, 105-111.
http://dx.doi.org/10.1016/j.bioelechem.2014.05.001
---------- CHICAGO ----------
Olaiz, N., Signori, E., Maglietti, F., Soba, A., Suárez, C., Turjanski, P., et al. "Tissue damage modeling in gene electrotransfer: The role of pH" . Bioelectrochemistry 100 (2014) : 105-111.
http://dx.doi.org/10.1016/j.bioelechem.2014.05.001
---------- MLA ----------
Olaiz, N., Signori, E., Maglietti, F., Soba, A., Suárez, C., Turjanski, P., et al. "Tissue damage modeling in gene electrotransfer: The role of pH" . Bioelectrochemistry, vol. 100, 2014, pp. 105-111.
http://dx.doi.org/10.1016/j.bioelechem.2014.05.001
---------- VANCOUVER ----------
Olaiz, N., Signori, E., Maglietti, F., Soba, A., Suárez, C., Turjanski, P., et al. Tissue damage modeling in gene electrotransfer: The role of pH. Bioelectrochemistry. 2014;100:105-111.
http://dx.doi.org/10.1016/j.bioelechem.2014.05.001