V-008 | Therapeutic approaches for peripheral nerve regeneration through a hybrid platform combining cell therapy and nanotechnology.

Cellular and Molecular Neurobiology
Author: David Oscar Donalisio | Email: daviddonalisio@gmail.com

David Oscar Donalisio^1°2°, Juan Orosco^3°,Vanina Usach^1°2°, Eliza De Sousa^3°, Romina Glisoni^4°, Pedro Mendoza Zélis^3°, Patricia Setton-Avruj^1°2°

^1° Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica. Cátedra de Química Biológica Patológica.
^2° Instituto de Química y Fisicoquímica Biológicas “Dr Alejandro C. Paladini” (IQUIFIB), UBA-CONICET.
^3° Instituto de Física La Plata (IFLP), UNLP-CONICET
^4° Instituto NANOBIOTEC UBA-CONICET. Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Peripheral nerve injuries are frequent afflictions in which full recovery cannot be achieved employing current treatments. Our group focuses on the development of nanotechnological approaches to promote nerve regeneration in a rat model of Wallerian degeneration promoted by sciatic nerve crush. To this end we developed a hybrid platform, consisted of bone marrow mononuclear cells (BMMC) transfected with poly-lactic-co-glycolic acid nanocapsules (PLGA-NC), functionalized with polyethyleneimine (PEI) and loaded with magnetic nanoparticles (MNP), for magnetic targeting of the systemically transplanted platform to the lesion area. Both PLGA-NC and MNP were characterized by thermogravimetry, vibrating-sample magnetometer, transmission electron microscopy and dynamic light scattering. To generate the hybrid platform BMMC are transfected with PLGA-NC:PEI:DNA (mock plasmid) loaded with MNPs and labeled with a fluorochrome. Following rat sciatic nerve crush the platform is systemically transplanted and magnetically targeted to the injured nerve. Seven days post-treatment behavioral tests are performed to assess the effects of the hybrid platform. Our results suggest that the hybrid platform does not hinder the analgesic effects of BMMC, which is optimized by magneto targeting.
Future experiments employing the hybrid platform containing NGF or BDNF mRNA will be performed to evaluate a potential therapeutic approach, and to better understand peripheral nerve regeneration mechanisms.