Ben M'Barek Karim, Regent Florian, Monville Christelle
Karim Ben M'Barek, Florian Regent, Christelle Monville, INSERM UMR861, I-Stem, AFM, Genopole Campus 1, 91030 Evry, France.
World J Stem Cells. 2015 Apr 26;7(3):596-604. doi: 10.4252/wjsc.v7.i3.596.
Human cell types affected by retinal diseases (such as age-related macular degeneration or retinitis pimentosa) are limited in cell number and of reduced accessibility. As a consequence, their isolation for in vitro studies of disease mechanisms or for drug screening efforts is fastidious. Human pluripotent stem cells (hPSCs), either of embryonic origin or through reprogramming of adult somatic cells, represent a new promising way to generate models of human retinopathies, explore the physiopathological mechanisms and develop novel therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induce pluripotent stem cells together with the continuous improvement of methods to differentiate these cells into disease-affected cellular subtypes opens new perspectives to model and understand a large number of human pathologies, including retinopathies. This review focuses on the added value of hPSCs for the disease modeling of human retinopathies and the study of their molecular pathological mechanisms. We also discuss the recent use of these cells for establishing the validation studies for therapeutic intervention and for the screening of large compound libraries to identify candidate drugs.
受视网膜疾病(如年龄相关性黄斑变性或色素性视网膜炎)影响的人类细胞类型数量有限且难以获取。因此,为了进行疾病机制的体外研究或药物筛选而分离这些细胞非常困难。人类多能干细胞(hPSC),无论是来源于胚胎还是通过重编程成年体细胞获得,都代表了一种生成人类视网膜病变模型、探索生理病理机制以及开发新型治疗策略的新的有前景的方法。疾病特异性人类胚胎干细胞是最早用于研究某些疾病状态的材料来源。最近有研究表明,人类体细胞,如成纤维细胞或血细胞,可以被基因转化为诱导多能干细胞,同时将这些细胞分化为受疾病影响的细胞亚型的方法也在不断改进,这为建模和理解包括视网膜病变在内的大量人类疾病开辟了新的视角。本综述重点关注hPSC在人类视网膜病变疾病建模及其分子病理机制研究方面的附加价值。我们还讨论了这些细胞最近在建立治疗干预验证研究以及筛选大型化合物库以鉴定候选药物方面的应用。