Inserm U 861, I-STEM, AFM, 91030, Evry cedex, France.
Regen Med. 2011 Sep;6(5):607-22. doi: 10.2217/rme.11.46.
Considerable hope surrounds the use of disease-specific pluripotent stem cells, which can differentiate into any cell type, as starting materials to generate models of human disease that will allow exploration of pathological mechanisms and the search for new treatments. Disease-specific human embryonic stem cells have provided a useful source for studying certain disease states. However, reprogramming of human somatic cells that use readily accessible tissue, such as skin or blood, to generate embryonic-like induced pluripotent stem cells has opened new perspectives for modeling and understanding a larger number of human pathologies. Here, we examine the challenges in creating a disease model from human pluripotent stem cells, and describe their use to model both cell-autonomous and non-cell-autonomous mechanisms, the need for adequate control experiments and the genetic limitations of human induced pluripotent stem cells. Progress in these areas will substantially accelerate effective application of disease-specific human pluripotent stem cells for drug screening.
人们对利用疾病特异性多能干细胞寄予厚望，这些细胞可以分化为任何细胞类型，可作为起始材料来生成人类疾病模型，从而能够探索病理机制并寻找新的治疗方法。疾病特异性人类胚胎干细胞为研究某些疾病状态提供了有用的来源。然而，通过对易于获取的组织（如皮肤或血液）中的人类体细胞进行重编程，生成类似胚胎的诱导多能干细胞，为模型构建和理解更多的人类疾病开辟了新的视角。在这里，我们探讨了用人多能干细胞创建疾病模型所面临的挑战，并描述了它们在模拟细胞自主和非细胞自主机制中的应用，还讨论了对充分的对照实验的需求以及人类诱导多能干细胞的遗传局限性。这些领域的进展将极大地促进特定疾病的人类多能干细胞在药物筛选中的有效应用。
