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Ivan Fernandez-Bueno, Sonia Labrador, Maria Teresa Garcia-Gutierrez, Girish Kumar Srivastava, Jose-Carlos Pastor; Mesenchymal stem cells reduce neuroretinal degeneration in vitro. Invest. Ophthalmol. Vis. Sci. 2018;59(9):540. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cell-based therapies offer an all-encompassing approach, through paracrine effects (immunomodulation, neuroprotection and tissue repair), for neurodegenerative diseases. The purpose of this study was to evaluate Mesenchymal Stem Cells (MSCs) capability to reduce spontaneous neuroretina (NR) degeneration in culture.
Human bone marrow MSCs were commercially provided by Citospin S.L. (Valladolid, Spain). These cells are approved by the Spanish Drug Agency for autologous and allogenic use in human clinical trials. NR explants were obtained from the area centralis of porcine eyes (local slaughterhouse). NR explants were cultured alone (controls) or supplemented with MSCs in the same culture-well but physically separated by the culture membrane. Cultures were maintained during 72 hours and samples were processed for paraffin wax embedding. Fresh NR samples were also processed. NR sections were stained for hematoxylin and eosin or immunostained for TUNEL, glial fibrillary acidic protein, tubulin beta III and neuronal nuclei. Retinal morphometry, apoptosis rate, glial activation degree and retinal ganglion cells were evaluated. Mean statistical analysis were performed with ANOVA of repeated measurements. Statistical significance level was set at 5%.
Samples cultured for 72 hours showed spontaneous morphological degenerative changes already characterized by our group (Di Lauro S, et al. IOVS 2014;55:ARVO E-Abstract 6314). However, when cocultured with human MSCs, NR preserve better morphology, exhibited fewer TUNEL-positive cells, showed minor reactive gliosis, and preserved retinal ganglion cells from degenerative processes (all p<0.05).
Human MSCs preserve porcine NR from spontaneous degeneration in coculture. These results are potentially related to the secretion and diffusion of neurotrophic factors from the MSCs to the NR, as previously pointed out by our group (Labrador-Velandia S, et al. IOVS 2017;58:ARVO E-Abstract 4565). Therefore, MSCs are potentially effective as neuroprotective therapy via their paracrine effects. These findings enable future research to explore the intravitreal use of commercially prepared MSCs for both retinal and optic nerve degenerative diseases.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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