Schakman, O. (Olivier)
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- Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury(Elsevier, 2013) Blanco-Prieto, M.J. (María José); Jankovski, A. (Aleksandar); Ansorena-Artieda, E. (Eduardo); Preat, V. (Veronique); Rieux, A. (Anne) des; Berdt, P. (Pauline) de; Jacobs, D. (Damien); Deumens, R. (Ronald); Ucakar, B. (Bernard); Schakman, O. (Olivier); Simon-Yarza, T. (Teresa)We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low III tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals.
- Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord(Wiley-Blackwell, 2013) Clotman, F. (Frederic); Audouard, E. (Emilie); Bailly, Ch. (Christian); Blanco-Prieto, M.J. (María José); Feron, O. (Olivier); Ansorena-Artieda, E. (Eduardo); Preat, V. (Veronique); Auhl, D. (Dietmar); Bouzin, C. (Caroline); Rieux, A. (Anne) des; Berdt, P. (Pauline) de; Jacobs, D. (Damien); Ucakar, B. (Bernard); Schakman, O. (Olivier); Carmeliet, P. (Peter); Simon-Yarza, T. (Teresa)We hypothesized that VEGF-containing hydrogels that gelify in situ following injection into a traumatized spinal cord, could stimulate spinal cord regeneration. Injectable hydrogels composed of 0.5% MVG alginate, supplemented or not with fibrinogen, were used. The addition of fibrinogen to alginate had no effect on cell proliferation in vitro but supported neurite growth ex vivo. When injected into a rat spinal cord in a hemisection model, alginate supplemented with fibrinogen was well tolerated. The release of VEGF that was incorporated into the hydrogel was influenced by the VEGF formulation (encapsulated in microspheres or in nanoparticles or in solution (free)). A combination of free VEGF and VEGF-loaded nanoparticles was mixed with alginate:fibrinogen and injected into the lesion of the spinal cord. Four weeks post-injection injection, angiogenesis and neurite growth were increased compared to hydrogel alone. The local delivery of VEGF by injectable alginate:fibrinogen-based hydrogel induced some plasticity in the injured spinal cord involving fiber growth into the lesion site.