Generation of Retinal Organoids with Mature Rods and Cones from Urine-Derived Human Induced Pluripotent Stem Cells.

Generation of Retinal Organoids with Mature Rods and Cones from Urine-Derived Human Induced Pluripotent Stem Cells.
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从尿液衍生的人诱导多能干细胞中生成具有成熟视杆细胞和视锥细胞的视网膜类器官

DOI:
10.1155/2018/4968658
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发表时间:
2018
影响因子:
4.3
通讯作者:
Zhong X
Zhong X
中科院分区:
医学3区
文献类型:
--
作者:
Li G;Xie B;He L;Zhou T;Gao G;Liu S;Pan G;Ge J;Peng F;Zhong X

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尿细胞,一种人体垃圾,已经成功地被重新编程为人类诱导的多能干细胞(U-hiPSCs),这在再生医学中有着巨大的前景。然而,目前尚不清楚U-hiPSCs能否或在多大程度上能够产生视网膜细胞。在不添加维甲酸(RA)的改良视网膜分化方案下,我们的研究表明U-hiPSCs能够向视网膜命运分化,并形成含有层状神经视网膜的3D视网膜器官,所有类型的视网膜细胞都位于体内适当的层中。更重要的是,U-hiPSCs产生了所有亚型的高度成熟的光感受器,甚至是富含红色/绿色锥体的光感受器。我们的数据表明,在培养液中添加RA对于U-hiPSC来源的光感受器的成熟和规范是不必要的,至少在视网膜类器官的壁龛中是这样。U-hiPSCs视网膜分化的成功为细胞治疗、疾病建模和药物筛选提供了许多机会,特别是在视网膜疾病的个性化药物治疗中,因为尿细胞可以非侵入性地从患者及其亲属那里收集。
Urine cells, a body trash, have been successfully reprogrammed into human induced pluripotent stem cells (U-hiPSCs) which hold a huge promise in regenerative medicine. However, it is unknown whether or to what extent U-hiPSCs can generate retinal cells so far. With a modified retinal differentiation protocol without addition of retinoic acid (RA), our study revealed that U-hiPSCs were able to differentiate towards retinal fates and form 3D retinal organoids containing laminated neural retina with all retinal cell types located in proper layer as in vivo. More importantly, U-hiPSCs generated highly mature photoreceptors with all subtypes, even red/green cone-rich photoreceptors. Our data indicated that a supplement of RA to culture medium was not necessary for maturation and specification of U-hiPSC-derived photoreceptors at least in the niche of retinal organoids. The success of retinal differentiation with U-hiPSCs provides many opportunities in cell therapy, disease modeling, and drug screening, especially in personalized medicine of retinal diseases since urine cells can be noninvasively collected from patients and their relatives.
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