Retinal pigment epithelium (RPE) is a critical cell monolayer forming the blood-retina-barrier (BRB) and a permeable bridge between the choriocapillaris and the retina. RPE is also crucial in maintaining photoreceptor function and for completing the visual cycle. Loss of the RPE is associated with the development of degenerative diseases like age-related macular degeneration (AMD). To treat diseases like AMD, pluripotent stem cell-derived RPE (pRPE) has been recently explored extensively as a regenerative module. pRPE like other ectodermal tissues requires specific lineage differentiation and long-term in vitro culturing for maturation. Therefore, understanding the differentiation process of RPE could be useful for stem cell-based RPE derivation. Developing pRPE-based transplants and delivering them into the subretinal space is another aspect that has garnered interest in the last decade. In this review, we discuss the basic strategies currently employed for stem cell-based RPE derivation, their delivery, and recent clinical studies related to pRPE transplantation in patients. We have also discussed a few limitations with in vitro RPE culture and potential solutions to overcome such problems which can be helpful in developing functional RPE tissue.

Center for Eye Research and Innovative Diagnostics Department of Ophthalmology Institute for Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway

Department of Biomaterials and Bioanalogous Systems Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic Prague Czech Republic

Department of Medical Biochemistry Institute of Clinical Medicine University of Oslo Oslo Norway

Department of Neuroregeneration Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic

Department of Ophthalmology Justus Liebig University Giessen University Hospital Giessen and Marburg GmbH Giessen Germany

Department of Ophthalmology Karl Landsteiner Institute for Retinal Research and Imaging Vienna Austria

Department of Ophthalmology Oslo University Hospital Oslo Norway

Department of Ophthalmology University of Split School of Medicine and University Hospital Centre Split Croatia

Laboratory of Cell Regeneration and Cell Plasticity Institute of Animal Physiology and Genetics Academy of Sciences of the Czech Republic Libechov Czech Republic

Ocular and Stem Cell Translational Research National Eye Institute National Institutes of Health Bethesda MD USA

Research Center Principe Felipe Stem Cell Therapies in Neurodegenerative Diseases Laboratory Valencia Spain

Stem Cell and Molecular Biology Laboratory Department of Biotechnology Bhupat and Jyoti Mehta School of Biosciences Indian Institute of Technology Madras Chennai Tamil Nadu India

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