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Neuroprotective effects of intravitreal injection of transgenic mesenchymal stem cells expressing hIGF-1 in mouse visual system after optic nerve crush
Introduction: Retinal ganglion cells (RGC), like other central nervous system neurons, have reduced regenerative capacity and, once damaged, the axons of adult RGC do not regenerate at long distances through the optic nerve. In addition, RGCs are extremely sensitive to axonal damage and most of them die after injury to the optic nerve. There are, currently, no clinically applicable therapies capable of protecting RGC and increasing the regeneration of their axons in an efficient and prolonged way. Recently, bone marrow-derived cells have been used to increase regeneration and/or functional recovey in several animal models of neurological diseases. In visual system, mesenchymal stem cells (MSC) were able to increase the survival of RGC in glaucoma models and after axonal transection or optic nerve crush, as demonstrated by several previous studies, including from our group. However, even inducing a significant increase in survival and regeneration of RGC, MSC therapy was not able to promote functional recovery.
Objetivos - Metodologia - Resultados - Discussão dos Resultados/Objectives - Methodology - Results - Discussion of Results/Objetivos - Metodología - Resultados - Discusión de los resultados
Objectives: In this work our main objective is to potentiate the regenerative response of cell therapy through the use of a mouse transgenic MSC line expressing the human trophic factor IGF-1 (mMSC-hIGF1), which has neuroprotective and neuroregenerative action. Methodology: SvEv129 adult mice were submitted to optic nerve crush and intravitreal injection of vehicle or 90,000 or 200,000 mMSC-hIGF1/control-mMSC. 14 days after surgery retinas were dissected and immunohistochemistry for TUJ1, marker of RGC, was performed. Results and discussion: Intravitreal injection of 90,000 mMSC-IGF1 cells after optic nerve crush was enough to induce the same significant neuroprotection evoked by 200,000 control-mMSC, leading to an increase of about 45% in the number of RGC compared to animals treated with PBS. Injection of 200,000 mMSC-hIGF1 promoted an even more robust and significant neuroprotective response, with an increase of about 90% in the number of RGC detected in relation to the PBS group.
Considerações Finais/Final considerations/Consideraciones finales
Conclusions: These data suggest that IGF-1 expression is capable of significantly potentiate the neuroprotective action of MSCs. It remains to be determined whether this effect is sustained after long periods and if it also results in an increase in axonal regeneration through the optic nerve and visual function recovery.
Palavras-chave/Key words/Palabras clave
Mesenchymal Stem Cells
Optic Nerve Crush
Mesenchymal stem cells/adultas
JULIANA FERREIRA VASQUES, Carla Andreia Abreu, Bruno Solano F Souza, Milena B P Soares, Rosalia Mendez-Otero