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Ivan Fernandez-Bueno, M Luz Alonso-Alonso, Maria Teresa Garcia-Gutierrez, Girish Kumar Srivastava, Jose-Carlos Pastor; Mesenchymal stem cells conditioned medium produced on nicotinamide and/or vasoactive intestinal peptide action improve antioxidative/neuroprotective properties in vitro. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3343.
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© ARVO (1962-2015); The Authors (2016-present)
Mesenchymal Stem Cells (MSC) have paracrine properties which make them suitable to develop potential MSC-based therapies without the need to perform stem cell transplants. The purpose of this study was to evaluate the potential antioxidative and neuroprotective properties of various pharmaceutical compositions, based on conditioned medium (CM) of adipose-MSC (aMSC-CM) produced on nicotinamide (NIC) and/or vasoactive intestinal peptide (VIP) actions, in retinal degeneration models.
Nine pharmaceutical compositions were obtained from three different experimental conditions: 1) aMSCs-CM combined with NIC, VIP or NIC+VIP (n=3); 2) aMSCs-CM produced by aMSCs stimulation with the mentioned drugs (n=3); and 3) aMSCs-CM produced by aMSCs stimulation and combination with the mentioned drugs (n=3). Then, antioxidative properties of the 9 compositions were evaluated in an oxidative stress model of retinal pigment epithelium cells (ARPE-19). Cell recovery and proliferation were quantified. Then, neuroprotective properties of previously selected compositions were evaluated in neuroretinal organotypic cultures. Morphometric modifications and glial activation degree were evaluated. Statistical analysis was performed by ANOVA of repeated measurements and Welch test. Statistical significance level was set at 5%.
aMSCs-CM stimulated or stimulated/combined with NIC or NIC+VIP showed potential to increase recovery and proliferation of stressed ARPE-19 cells. Neurorretina explants exposed to aMSCs-CM stimulated/combined with NIC+VIP showed better preservation of the neuroretinal morphology with the lowest levels of glial activation.
The antioxidative and neuroprotective properties of aMSCs-CM are enhanced when aMSCs were stimulated/combined with NIC+VIP actions. These results emphasize the potential of MSC-based therapies, without the need to inject cells into the eye, through the combinations of MSC paracrine secretions and exogenous drugs.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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