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

Simple item page
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorUrzúa, Cristhian
dc.contributor.authorMontecino, Scarleth
dc.contributor.authorLeal, Karla
dc.contributor.authorConget, Paulette
dc.contributor.authorEzquer, Fernando
dc.date.accessioned2017-01-04T15:39:50Z
dc.date.available2017-01-04T15:39:50Z
dc.date.issued2016
dc.descriptionCentro de Medicina Regenerativa
dc.description.abstractDiabetic 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.
dc.identifier.citationEzquer M, Urzua CA, Montecino S, Leal K, Conget P, Ezquer F. Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice. Stem Cell Res Ther. 2016 Mar 16;7:42.
dc.identifier.urihttp://hdl.handle.net/11447/921
dc.identifier.urihttp://dx.doi.org/ 10.1186/s13287-016-0299-y
dc.language.isoen_US
dc.publisherBioMed Central
dc.subjectCytoprotection
dc.subjectDiabetes
dc.subjectDiabetic retinopathy
dc.subjectMesenchymal stem cells
dc.subjectMicroenvironment
dc.subjectMultipotent mesenchymal stromal cells
dc.subjectPrevention
dc.subjectRetinal ganglion cells
dc.titleIntravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microenvironment in the retina of diabetic mice
dc.typeArtículo

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Intravitreal administration of multipotent mesenchymal stromal cells triggers a cytoprotective microen....pdf
Size:
3.68 MB
Format:
Adobe Portable Document Format
Description:
Artículo completo
Download

Collections

Artículos Medicina y Ciencias de la Salud

Implementado por OpenGeek Services