4 research outputs found
Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy
Modelo animal; Medicina regenerativa; RetinaModel animal; Medicina regenerativa; RetinaAnimal model; Regenerative medicine; RetinaBackground: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA.This work was supported by Spanish Ministry of Science and Innovation (MICINN, RTI2018-095377-B-100), Instituto de Salud Carlos III ISCIII/FEDER (PRB2 PT13/0001/0041; TerCel RD16/0011/0024 and Oftared-RETICS RD16/0008), ERA-NET EuroNanoMed III/ISCIII (AC19/00080), the Catalan Government, AGAUR (2017-SGR-899), CERCA Programme/Generalitat de Catalunya, and by Fundació Carmen i Mª José Godó (Fundació CMJ Godó 2017)
Transplantation of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium in a Swine Model of Geographic Atrophy
Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA. Keywords: age-related macular degeneration (AMD); geographic atrophy; pig; animal model; stem cells; iPSC; RPE; retina; regenerative medicine; advanced cell therap
Kinetics of Heterogeneous Background in Stargardt’s Disease over Time
Stargardt’s disease (STGD1) is caused by mutations in the ABCA4 gene. Different lesions characterised by decreased autofluorescence levels are found in fundus autofluorescence (FAF) from STGD1 patients and could be used as outcome indicators for disease progression. We investigated the fate of foci with reduced autofluorescence (FRA) within the heterogeneous background of STGD1 patients using FAF imaging. Genetically confirmed STGD1 patients presenting heterogeneous background autofluorescence on high-quality FAF images at a minimum of two visits at least 12 months apart were chosen. A grid centred on the fovea was used to define five different zones. Within each zone, five FRA were randomly selected for each eye. The eccentricity of foci was determined at different time points for each patient. Analysis of 175 randomly chosen FRA showed consistent centrifugal displacement over time, most notably in eyes showing areas with definitely decreased autofluorescence. Interestingly, FRA did not leave an area of hypo-autofluorescence on FAF in locations where they were previously located. These findings may help to better understand STGD1 progression, improve FAF interpretation, and shed light on the nature of heterogeneous background