Human Mesenchymal Stem Cell Secretome Exhibits a Neuroprotective Effect over In Vitro Retinal Photoreceptor Degeneration

Retinal photoreceptor degeneration occurs frequently in several neurodegenerative retinal diseases such as age-related macular degeneration, retinitis pigmentosa, or genetic retinal diseases related to the photoreceptors. Despite the impact on daily life and the social and economic consequences, there is no cure for these diseases. Considering this, cell-based therapy may be an optimal therapeutic option. This study evaluated the neuroprotective in vitro potential of a secretome of human bone marrow mesenchymal stem cells (MSCs) for retinal photoreceptors in vitro. We analyzed the photoreceptor morphologic changes and the paracrine factors secreted by human bone marrow MSCs in a physically separated co-culture with degenerated neuroretinas, using organotypic neuroretinal cultures. The results showed that the secretome of human bone marrow MSCs had a neuroprotective effect over the neuroretinal general organization and neuropreserved the photoreceptors from degeneration probably by secretion of neuroprotective proteins. The study of the expression of 1,000 proteins showed increased paracrine factors secreted by MSCs that could be crucial in the neuroprotective effect of the stem cell secretome over in vitro retinal degeneration. The current results reinforce the hypothesis that the paracrine effect of the human bone marrow MSCs may slow photoreceptor neurodegeneration and be a therapeutic option in retinal photoreceptor degenerative diseases.
This work was supported by grants from Fondo Europeo de Desarrollo Regional (FEDER) and Consejería de Educación from Junta de Castilla y León, Spain (grant VA077P17), and from the Spanish Health Institute Carlos III (ISCIII) (grants PI17/01930 and CB16/12/00400). The Proteomics Unit belongs to ProteoRed (PRB3-ISCIII) supported by grant PT17/0019/0023, of the PEI+D+I 2017-2020, funded by ISCIII and FEDER. R.U.-M. was supported by FEDER and Consejería de Educación from Junta de Castilla y León, Spain (grant VA077P17); K.P.-N. was supported by Fundación Carolina, Madrid, Spain; and I.F.-B. was supported by Centro en Red de Medicina Regenerativa y Terapia Celular, Junta de Castilla y León, Spain.