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Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice

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dc.contributor.author Ezquer, Marcelo
dc.contributor.author Urzúa, Cristhian
dc.contributor.author Montecino, Scarleth
dc.contributor.author Leal, Karla
dc.contributor.author Conget, Paulette
dc.contributor.author Ezquer, Fernando
dc.date.accessioned 2017-01-04T15:39:50Z
dc.date.available 2017-01-04T15:39:50Z
dc.date.issued 2016
dc.identifier.citation Stem Cell Research & Therapy, March 2016, n°7, p.42 es_CL
dc.identifier.uri http://dx.doi.org/ 10.1186/s13287-016-0299-y es_CL
dc.identifier.uri http://hdl.handle.net/11447/921
dc.description Centro de Medicina Regenerativa es_CL
dc.description.abstract Diabetic retinopathy is a common complication of diabetes and the leading cause of irreversible vision loss in the Western world. The reduction in color/contrast sensitivity due to the loss of neural cells in the ganglion cell layer of the retina is an early event in the onset of diabetic retinopathy. Multipotent mesenchymal stromal cells (MSCs) are an attractive tool for the treatment of neurodegenerative diseases, since they could differentiate into neuronal cells, produce high levels of neurotrophic factors and reduce oxidative stress. Our aim was to determine whether the intravitreal administration of adipose-derived MSCs was able to prevent the loss of retinal ganglion cells in diabetic mice. METHODS: Diabetes was induced in C57BL6 mice by the administration of streptozotocin. When retinal pro-damage mechanisms were present, animals received a single intravitreal dose of 2 × 10(5) adipose-derived MSCs or the vehicle. Four and 12 weeks later we evaluated: (a) retinal ganglion cell number (immunofluorescence); (b) neurotrophic factor levels (real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA)); (c) retinal apoptotic rate (TUNEL); (d) retinal levels of reactive oxygen species and oxidative damage (ELISA); (e) electrical response of the retina (electroretinography); (f) pro-angiogenic and anti-angiogenic factor levels (RT-qPCR and ELISA); and (g) retinal blood vessels (angiography). Furthermore, 1, 4, 8 and 12 weeks post-MSC administration, the presence of donor cells in the retina and their differentiation into neural and perivascular-like cells were assessed (immunofluorescence and flow cytometry). RESULTS: MSC administration completely prevented retinal ganglion cell loss. Donor cells remained in the vitreous cavity and did not differentiate into neural or perivascular-like cells. Nevertheless, they increased the intraocular levels of several potent neurotrophic factors (nerve growth factor, basic fibroblast growth factor and glial cell line-derived neurotrophic factor) and reduced the oxidative damage in the retina. Additionally, MSC administration has a neutral effect on the electrical response of the retina and did not result in a pathological neovascularization. CONCLUSIONS: Intravitreal administration of adipose-derived MSCs triggers an effective cytoprotective microenvironment in the retina of diabetic mice. Thus, MSCs represent an interesting tool in order to prevent diabetic retinopathy. es_CL
dc.language.iso en_US es_CL
dc.publisher BioMed Central es_CL
dc.subject Cytoprotection es_CL
dc.subject Diabetes es_CL
dc.subject Diabetic retinopathy es_CL
dc.subject Mesenchymal stem cells es_CL
dc.subject Microenvironment es_CL
dc.subject Multipotent mesenchymal stromal cells es_CL
dc.subject Prevention es_CL
dc.subject Retinal ganglion cells es_CL
dc.title Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice es_CL
dc.type Artículo es_CL


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