INVESTIGADORES
TURJANSKI Pablo Guillermo
congresos y reuniones científicas
Título:
Tissue damage in vaccination protocols based on electroporation: pH fronts and tissue natural buffering
Autor/es:
MARINO, M.; OLAIZ, N.; SIGNORI, E.; MAGLIETTI, F.; SUAREZ, C.; COLOMBO, L.; TURJANSKI, P.; MICHINSKI, S.; LUJAN, E.; MARSHALL, G.
Lugar:
Roma
Reunión:
Conferencia; The 14th International Conference on Progress in Vaccination against Cancer; 2014
Resumen:
Gene electrotransfer vaccination protocols (GET) constitute a safe and powerful way for introducing foreign antigens into the host for inducing an immune response. Optimal GET requires a compromise between maximum transgene expression and minimal tissue damage. ThoughGET in skeletal muscle can be improved by pretreatment with hyaluronidase, tissue damage remains severe close to the electrodes, with a concomitant loss of GET efficiency [1]. In previous works [2, 3] it was shown that pH fronts generated by GET protocols produced non negligible pH changes and that these changes were the principalcause of tissue damage. Here we analyze the role of pH in the presence of tissue bicarbonate buffering system in tissue damage in GET protocolsthrough in silico modeling using the Poisson-Nernst-Planck equations for ion transport. The model is contrasted with experimental measurements using intravital microscopy in a dorsal skinfold chamber (DSC). Theoretical modeling confirms experimental measurements and shows that in GET protocols whether with or without hyaluronidase pretreatment, regardless of the presence of tissue natural buffer attenuation, pH fronts are the principal cause of muscle damage near theelectrodes.electrodes.[1] J. M. McMahon, E. Signori, K. E. Wells, V. M.Fazio, D. J. Wells, Optimizationof electrotransfer of plasmid into skeletal muscle bypretreatment with hyaluronidase - increasedexpression with reduced muscle damage, GeneTherapy 8 (2001) 1264{1270. PMID: 11509960.[2] Maglietti F, Michinski S, Olaiz N, Castro M,Suárez C and G. Marshall, The Role of Ph Fronts inTissue Electroporation Based Treatments. PLoSONE 8(11): e80167.doi:10.1371/journal.pone.0080167 (2013).[3] N. Olaiz, E. Signori, F. Maglietti, A. Soba, C.Suárez, P. Turjanski, S. Michinski, G. Marshall,Tissue damage modeling in plasmid geneelectrotransfer: the role of pH (2014)http://dx.doi.org/10.1016/j.bioelechem.2014.05.001]