INTRODUCTION: Combinatory strategies using pharmacology and stem cell therapy have emerged due to their potential in the treatment of retinal pigment epithelium (RPE) cell related diseases, and a variety of different stem cell sources have been evaluated both in animal models and in humans. RPE cells derived from human embryonic stem cells (hESCs) and human induced pluripotent cells (hiPSCs) are already in clinical trials, holding great promise for the treatment of age-related macular disease (AMD) and hereditary RPE-related retinal dystrophies. Highly efficient protocol for RPE generations have been developed, but they are still time-consuming and laborious. Areas covered: The authors review RPE related diseases, as well as the known functions of RPE cells in retinal homeostasis. The authors also discuss small molecules that target RPE in vivo as well as in vitro to aid RPE differentiation from pluripotent stem cells clinically. The authors base this review on literature searches performed through PubMed. Expert opinion: Using high-throughput systems, technology will provide the possibility of identifying and optimizing molecules/drugs that could lead to faster and simpler protocols for RPE differentiation. This could be crucial in moving forward to create safer and more efficient RPE-based personalized therapies.

b Institute of Macromolecular Chemistry Czech Academy of Sciences Praha 6 Czech Republic

c Institute of Experimental Medicine Department of Tissue Cultures and Stem Cells Czech Academy of Sciences Prague Czech Republic

Laboratory of Cell Regeneration and Plasticity Research Center PIGMOD Institute of Animal Physiology and Genetics Czech Academy of Sciences Libechov Czech Republic

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

Stem Cell Therapies in Neurodegenerative Diseases Lab Research Center Principe Felipe Valencia Spain c Institute of Experimental Medicine Department of Tissue Cultures and Stem Cells Czech Academy of Sciences Prague Czech Republic e National Stem Cell Bank Valencia Node Biomolecular and Bioinformatics Resources Platform PRB2 ISCIII Research Center Principe Felipe Valencia Spain

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$a Artero-Castro, Ana $u a Stem Cell Therapies in Neurodegenerative Diseases Lab , Research Center "Principe Felipe" , Valencia , Spain.

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$a The identification of small molecules that stimulate retinal pigment epithelial cells: potential novel therapeutic options for treating retinopathies / $c A. Artero-Castro, S. Popelka, P. Jendelova, J. Motlik, T. Ardan, FJ. Rodriguez Jimenez, S. Erceg,

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$a INTRODUCTION: Combinatory strategies using pharmacology and stem cell therapy have emerged due to their potential in the treatment of retinal pigment epithelium (RPE) cell related diseases, and a variety of different stem cell sources have been evaluated both in animal models and in humans. RPE cells derived from human embryonic stem cells (hESCs) and human induced pluripotent cells (hiPSCs) are already in clinical trials, holding great promise for the treatment of age-related macular disease (AMD) and hereditary RPE-related retinal dystrophies. Highly efficient protocol for RPE generations have been developed, but they are still time-consuming and laborious. Areas covered: The authors review RPE related diseases, as well as the known functions of RPE cells in retinal homeostasis. The authors also discuss small molecules that target RPE in vivo as well as in vitro to aid RPE differentiation from pluripotent stem cells clinically. The authors base this review on literature searches performed through PubMed. Expert opinion: Using high-throughput systems, technology will provide the possibility of identifying and optimizing molecules/drugs that could lead to faster and simpler protocols for RPE differentiation. This could be crucial in moving forward to create safer and more efficient RPE-based personalized therapies.

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$a Popelka, Stepan $u b Institute of Macromolecular Chemistry , Czech Academy of Sciences , Praha 6 , Czech Republic.

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$a Ardan, Taras $u d Laboratory of Cell Regeneration and Plasticity, Research Center PIGMOD , Institute of Animal Physiology and Genetics, Czech Academy of Sciences , Libechov , Czech Republic.

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$a Rodriguez Jimenez, Francisco Javier $u a Stem Cell Therapies in Neurodegenerative Diseases Lab , Research Center "Principe Felipe" , Valencia , Spain.

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$a Erceg, Slaven $u a Stem Cell Therapies in Neurodegenerative Diseases Lab , Research Center "Principe Felipe" , Valencia , Spain. c Institute of Experimental Medicine, Department of Tissue Cultures and Stem Cells , Czech Academy of Sciences , Prague , Czech Republic. e National Stem Cell Bank-Valencia Node, Biomolecular and Bioinformatics Resources Platform PRB2,ISCIII , Research Center "Principe Felipe" , Valencia , Spain.

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