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Xiufeng Zhong, Bingbing Xie, Guilan Li, Guangjin Pan, Jian Ge; Generation of 3D retinal tissues from urine-derived hiPSCs for treatment of retinal diseases. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal degenerative diseases are the major causes of vision loss without effective treatment so far. Human induced pluripotent stem cells (hiPSC) hold great promise for treating these diseases. Recently, we have demonstrated that hiPSCs generated from different somatic cells including fibroblasts, blood cells and skin cells can be guided to differentiate into retinal cells, even to form eye cups. However, it is still unclear whether hiPSCs derived from urine cells have the same potential of retinal differentiation. This study aims to explore the capability of urine-derived hiPSCs to generate retinal tissues in dish.
Urine-derived hiPSC lines, UE017 and UE005, were derived from Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences. Cells were maintained in feeder-free condition, and directed to differentiate into retinal cups with our published protocol (Zhong X, Nature Communication 2014). Morphological changes were closely observed under inverted microscope. Immunofluorescence was done with markers specific for the retinal cells, such as VSX2, HuC/D, Brn3 and Recoverin.
The urine-derived hiPSCs were able to differentiate into retinal cell lineages, from retinal progenitor cells expressing VSX2 and MCM2, to major retinal subtypes including retinal ganglion cells positive for Brn3 and islet 1, photoreceptor cells positive for recoverin and otx2 and retinal pigment epithelium (RPE). In addition, retinal progenitor cells generated from urine hiPSCs, under suspension culture condition, could self-form three dimensional retinal cups comprising a thick and transparent neural retina attached with a roll-up RPE ball.
Our results demonstrate that urine-derived hiPSCs have the similar potential of retinal differentiation as hiPSCs derived from other somatic cells, recapitulating the main steps of human retinal development in vivo. The success here with urine hiPSCs provides many opportunities in creating human eye disease model, drug screening and cell therapy since urine cells can be conveniently collected without any invasive procedure.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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