RT info:eu-repo/semantics/article
T1 Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures
A1 Labrador Velandia, Sonia Cecilia
A1 Alonso Alonso, María Luz
A1 Di Lauro, Salvatore
A1 García Gutiérrez, María Teresa
A1 Srivastava, Girish Kumar
A1 Pastor Jimeno, José Carlos
A1 Fernández Bueno, Iván
AB Through the paracrine effects of stem cells, including the secretion of neurotrophic, immunomodulatory, andanti-apoptotic factors, cell-based therapies offer a new all-encompassing approach to treatment of neurodegenerative diseases. In this study, we used physically separated co-cultures of porcine neuroretina (NR) and human mesenchymal stem cells (MSC) to evaluate the MSC paracrine neuroprotective effects on NR degen-eration. NR explants were obtained from porcine eyes and cultured alone or co-cultured with commerciallyavailable MSCs from Valladolid (MSCV; Citospin S.L.; Valladolid, Spain), currently used for several approvedtreatments. Cultures were maintained for 72h. MSC surface markers were evaluated before and after co-culturewith NRs. Culture supernatants were collected and the concentration of brain-derived neurotrophic factor(BDNF), ciliary neurotrophic factor (CNTF), and glial-derived neurotrophic factor (GDNF) were determined byenzyme-linked immunosorbent assays. NR sections were stained by haematoxylin/eosin or immunostained forterminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), glial fibrillary acidic protein, β-tubulinIII, and neuronal nuclei marker. NR morphology, morphometry, nuclei count, apoptosis rate, retinal ganglioncells, and glial cell activation were evaluated. Treatment effects were statistically analysed by parametric or non-parametric tests. The MSCs retained stem cell surface markers after co-culture with NR. BDNF and CNTF con-centrations in NR-MSCV co-cultures were higher than other experimental conditions at 72h (p< 0.05), but noGDNF was detected. NR general morphology, total thickness, and cell counts were broadly preserved in co-cultures, and the apoptosis rate determined by TUNEL assay was lower than for NR monocultures (all p< 0.05).Co-cultures with MSCV also protected retinal ganglion cells from degenerative changes and reduced reactivegliosis (both p< 0.05). In this invitromodel of spontaneous NR degeneration, the presence of co-cultured MSCsretarded neuroglial degeneration. This effect was associated with elevated concentrations of the neurotrophicfactors BDNF and CNTF. Our data suggest that the paracrine secretion of these, and possibly other molecules, area potential resource for the treatment of several neuroretinal diseases.
SN 0014-4835
YR 2019
FD 2019
LK https://uvadoc.uva.es/handle/10324/71458
UL https://uvadoc.uva.es/handle/10324/71458
LA eng
NO Experimental Eye Research 2019;185:107671
NO Producción Científica
DS UVaDOC
RD 14-mar-2025