Photoreceptor degenerative diseases are a major cause of blindness for which cell replacement is one of the most encouraging strategies. For stem cell-based therapy using human induced pluripotent stem cells (hiPSCs), it is crucial to obtain a homogenous photoreceptor cell population. We confirmed that the cell surface antigen CD73 is exclusively expressed in hiPSC-derived photoreceptors by generating a fluorescent cone rod homeobox (Crx) reporter hiPSC line using CRISPR/Cas9 genome editing. We demonstrated that CD73 targeting by magnetic-activated cell sorting (MACS) is an effective strategy to separate a safe population of transplantable photoreceptors. CD73+ photoreceptor precursors can be isolated in large numbers and transplanted into rat eyes, showing capacity to survive and mature in close proximity to host inner retina of a model of photoreceptor degeneration. These data demonstrate that CD73+ photoreceptor precursors hold great promise for a future safe clinical translation.
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http://dx.doi.org/10.1016/j.stemcr.2018.07.005 | DOI Listing |
Cell Mol Life Sci
February 2022
MediCity Research Laboratory and InFLAMES Flagship, University of Turku, Tykistökatu 6A, 20520, Turku, Finland.
ATP and adenosine have emerged as important signaling molecules involved in vascular remodeling, retinal functioning and neurovascular coupling in the mammalian eye. However, little is known about the regulatory mechanisms of purinergic signaling in the eye. Here, we used three-dimensional multiplexed imaging, in situ enzyme histochemistry, flow cytometric analysis, and single cell transcriptomics to characterize the whole pattern of purine metabolism in mouse and human eyes.
View Article and Find Full Text PDFJ Biol Chem
August 2021
Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan. Electronic address:
Membrane phospholipids play pivotal roles in various cellular processes, and their levels are tightly regulated. In the retina, phospholipids had been scrutinized because of their distinct composition and requirement in visual transduction. However, how lipid composition changes during retinal development remains unclear.
View Article and Find Full Text PDFOphthalmic Res
June 2021
Departments of Immunology and Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan,
Background: CCL2 (also known as monocyte chemoattractant protein 1) and CX3CR1 (also known as Fractalkine receptor)-deficient mice have damaged photoreceptors.
Objectives: We examined the interaction of SDF1 and CXCR4 on the differentiation of retinal progenitors into rhodopsin-positive photoreceptors.
Methods: Cloned retinal progenitors were obtained by Pax6 gene transfection of mouse iPS cells followed by serial dilution.
Toxicol In Vitro
March 2020
LVF Ophthalmology Research Centre, Translational Research Institute, Woolloongabba, QLD, Australia; Greenslopes Clinical School, Faculty of Medicine, University of Queensland, Greenslopes Hospital, Australia. Electronic address:
One of the major challenges in studying ocular toxicology is a lack of clinically-relevant retinal experimental models. In this study we describe the use of an in vitro human retinal explant strategy to generate a reproducible experimental model with utility in neuro-toxicity retinal studies. A retinal dissection strategy, referred to as the 8 fold quadrant dissection, was developed by dissecting human donor retinas into 4 fragments through the fovea in order to obtain 8 experimentally reproducible retinal explants from a single donor.
View Article and Find Full Text PDFStem Cell Reports
September 2018
Institut de la Vision, Sorbonne Université, INSERM, CNRS, 17, Rue Moreau, Paris 75012, France. Electronic address:
Photoreceptor degenerative diseases are a major cause of blindness for which cell replacement is one of the most encouraging strategies. For stem cell-based therapy using human induced pluripotent stem cells (hiPSCs), it is crucial to obtain a homogenous photoreceptor cell population. We confirmed that the cell surface antigen CD73 is exclusively expressed in hiPSC-derived photoreceptors by generating a fluorescent cone rod homeobox (Crx) reporter hiPSC line using CRISPR/Cas9 genome editing.
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