Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
Mol Psychiatry. 2017 Jun;22(6):808-819. doi: 10.1038/mp.2017.66. Epub 2017 Apr 4.
Two recent technologies, induced-pluripotent stem cells (iPSCs) and direct somatic reprogramming, have shown enormous potential for cell-based therapies against intractable diseases such as those that affect the central nervous system. Already, methods that generate most major cell types of the human brain exist. Whether the cell types are directly reprogrammed from human somatic cells or differentiated from an iPSC intermediate, the overview presented here demonstrates how these protocols vary greatly in their efficiencies, purity and maturation of the resulting cells. Possible solutions including micro-RNA switch technologies that purify target cell types are also outlined. Further, an update on the transition from 2D to 3D cultures and current organoid (mini-brain) cultures are reviewed to give the stem cell and developmental engineering communities an up-to-date account of the progress and future perspectives for modeling of central nervous system disease and brain development in vitro.
两种最近的技术,诱导多能干细胞(iPSCs)和直接体细胞重编程,在基于细胞的治疗方面显示出了巨大的潜力,可用于治疗诸如影响中枢神经系统的棘手疾病。目前已经存在生成人类大脑的大多数主要细胞类型的方法。无论细胞类型是直接从人类体细胞重编程得到的,还是从 iPSC 中间产物分化得到的,这里介绍的方法在效率、纯度和所得细胞的成熟度方面差异很大。还概述了包括微 RNA 开关技术在内的可能解决方案,该技术可纯化靶细胞类型。此外,还更新了从 2D 培养物到 3D 培养物的转变以及当前的类器官(迷你脑)培养物,以便向干细胞和发育工程界提供关于中枢神经系统疾病建模和体外脑发育的最新进展和未来展望。