Self-Formation of Optic Cups and Storable Stratified Neural Retina from Human ESCs
Self-Formation of Optic Cups and Storable Stratified Neural Retina from Human ESCs
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DOI：
10.1016/j.stem.2012.05.009
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发表时间：
2012-06-14
期刊：
影响因子：
23.9
通讯作者：
Sasai, Yoshiki
中科院分区：
文献类型：
--
作者：
Nakano, Tokushige;Ando, Satoshi;Sasai, Yoshiki
在本报告中，我们证明了在人类 ESC 培养中可以通过自组织形成视杯结构。人类 ESC 衍生的视杯比小鼠 ESC 衍生的视杯大得多，这可能反映了物种差异。人类ESC培养物中的神经视网膜较厚，并且自发地以顶端凸出的方式弯曲，这在小鼠ESC培养物中是看不到的。此外，人类ESC衍生的神经视网膜生长成含有视杆细胞和视锥细胞的多层组织，而视锥细胞分化在小鼠ESC培养物中很少见。 Notch 抑制可大大加速人 ESC 培养物中光感受器的积累。此外，我们还表明，优化的玻璃化方法能够对人类来源的分层神经视网膜进行整体冷冻保存。这种在耗时的分化过程中的中间步骤的存储方法为大规模制备临床级视网膜组织的质量控制提供了通用的解决方案。
In this report, we demonstrate that an optic cup structure can form by self-organization in human ESC culture. The human ESC-derived optic cup is much larger than the mouse ESC-derived one, presumably reflecting the species differences. The neural retina in human ESC culture is thick and spontaneously curves in an apically convex manner, which is not seen in mouse ESC culture. In addition, human ESC-derived neural retina grows into multilayered tissue containing both rods and cones, whereas cone differentiation is rare in mouse ESC culture. The accumulation of photoreceptors in human ESC culture can be greatly accelerated by Notch inhibition. In addition, we show that an optimized vitrification method enables en bloc cryopreservation of stratified neural retina of human origin. This storage method at an intermediate step during the time-consuming differentiation process provides a versatile solution for quality control in large-scale preparation of clinical-grade retinal tissues.