INVESTIGADORES
SETTON Clara Patricia
congresos y reuniones científicas
Título:
Transfected BMMC withPLGA nanocapsules loaded with iron oxide magnetic nanoparticles, a hybrid platform for peripheral nerve regeneration
Autor/es:
DAVID DONALISIO; MARCELA FERNANDEZ VAN RAAP; CLARA P. SETTON
Lugar:
CABA
Reunión:
Congreso; First Meeting Glia Club Southern Cone: The good, the bad, the nice and the ugly of glial cells.; 2022
Institución organizadora:
Club de la Glia
Resumen:
In the context of peripheral nerve injury, reaching full recovery is still difficult since there is a limitation associated with the short time window availablefor therapeutic intervention. Our group focuses on the development of new strategies to promote functional and morphological nerve regeneration andto prevent neuropathic pain development, using a reversible model of Wallerian degeneration obtained by crushing the rat sciatic nerve. In this model, we previously showed that magnetic targeting of systemically transplanted adipose derived mesenchymal stem cells loaded with iron oxide magnetic nanoparticles (MNP) optimizes the beneficial effect obtained with cells transplantalone [1].The aim of the present work wasto develop a hybrid platform consisting of a poly-lactic-co-glycolic acid (PLGA) nanocapsule loaded withMNP and functionalized with polyethyleneimine (PEI), useful for transfecting and magnetically labeling bone marrow mononuclear cells (BMMC) to be magnetically targeted to the injured sciatic nerve after their systemic transplant.To this end, MNP were synthesized by thermal decomposition, and nanocapsules of PLGA(fluorochrome/MNP) were prepared by the double emulsion evaporation technique. TheDynamic Light Scattering (DLS) analysisat 25ºC of PLGA nanocapsules, showed monodisperse nanometric sizes in the range of 220 and 240 nm andPDI valuesbetween 0.110 and 0.130. The generation of PLGA:PEI:pDNA complex was confirmed by an electrophoretic retention assay achieving full retention for a relation 6:3:5, and the reversibility of PEI:pDNA interaction was checked with heparin. BMMC transfection was evaluated with epifluorescence microscopy in PLGA(rhodamine) or PLGA(FITC). Finally, the systemic transplant of the hybrid platform immediately after the lesion demonstrated the arrival of transfected cells to the injured sciatic nerve as wellas the effectiveness of their magnetic targeting. These results encourage us to evaluate if this hybrid platform may be a tool to assess the involvement of mRNA/pDNAof growth factors such as NGF, IGF-1, BDNF, GDNF or CNTF to better understand nerve regeneration mechanisms and to establish a potential therapeutic approach.[1] P. A. Soto et al. Acta Biomater., 130, 234-247, 2021