Oliveira Carolina Reis, Paiva Mayara Rodrigues Brandão de, Ribeiro Marcela Coelho Silva, Andrade Gracielle Ferreira, Carvalho Juliana Lott, Gomes Dawidson Assis, Nehemy Márcio, Fialho Sílvia Ligório, Silva-Cunha Armando, Góes Alfredo Miranda de
1Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Int J Stem Cells. 2021 Feb 28;14(1):74-84. doi: 10.15283/ijsc20094.
Eye diseases have a high socioeconomic impact on society and may be one of the fields in which most stem cell-related scientific accomplishments have been achieved recently. In this context, human Pluripotent Stem Cell (hPSC) technology arises as an important tool to produce and study human Embryonic Stem cell derived-Retinal Pigmented Epithelial Cells (hES-RPE) for several applications, such as cell therapy, disease modeling, and drug screening. The use of this technology in pre-clinical phases attends to the overall population desire for animal-free product development. Here, we aimed to compare hES-RPE cells with ARPE-19, one of the most commonly used retinal pigmented epithelial immortalized cell lines.
Functional, cellular and molecular data obtained suggest that hES-RPE cells more closely resembles native RPEs compared to ARPE-19. Furthermore, hES-RPE revealed an interesting robustness when cultured on human Bruch's membrane explants and after exposure to Cyclosporine (CSA), Sirolimus (SRL), Tacrolimus (TAC), Leflunomide (LEF) and Teriflunomide (TER). On these conditions, hES-RPE cells were able to survive at higher drug concentrations, while ARPE-19 cell line was more susceptible to cell death.
Therefore, hES-RPEs seem to have the ability to incur a broader range of RPE functions than ARPE-19 and should be more thoroughly explored for drug screening.
眼部疾病对社会具有较高的社会经济影响，并且可能是近年来在干细胞相关科学成就方面取得最多成果的领域之一。在此背景下，人类多能干细胞（hPSC）技术作为一种重要工具应运而生，可用于生产和研究人类胚胎干细胞衍生的视网膜色素上皮细胞（hES-RPE），以用于多种应用，如细胞治疗、疾病建模和药物筛选。在临床前阶段使用该技术符合总体人群对无动物产品开发的需求。在此，我们旨在比较hES-RPE细胞与ARPE-19（一种最常用的视网膜色素上皮永生化细胞系）。
获得的功能、细胞和分子数据表明，与ARPE-19相比，hES-RPE细胞与天然视网膜色素上皮细胞更相似。此外，hES-RPE在人布鲁赫膜外植体上培养以及暴露于环孢素（CSA）、西罗莫司（SRL）、他克莫司（TAC）、来氟米特（LEF）和特立氟胺（TER）后显示出有趣的稳健性。在这些条件下，hES-RPE细胞能够在更高的药物浓度下存活，而ARPE-19细胞系对细胞死亡更敏感。
因此，hES-RPE似乎比ARPE-19具有更广泛的视网膜色素上皮功能，并且应更深入地探索其用于药物筛选的潜力。
