Li Guilan, Xie Bingbing, He Liwen, Zhou Tiancheng, Gao Guanjie, Liu Shengxu, Pan Guangjin, Ge Jian, Peng Fuhua, Zhong Xiufeng
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Stem Cells Int. 2018 Jun 13;2018:4968658. doi: 10.1155/2018/4968658. eCollection 2018.
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.
尿液细胞，作为一种人体废弃物，已被成功重编程为人类诱导多能干细胞（U-hiPSC），这在再生医学领域有着巨大的前景。然而，迄今为止，尚不清楚U-hiPSC能否以及在多大程度上能够生成视网膜细胞。通过一种改良的不添加视黄酸（RA）的视网膜分化方案，我们的研究表明，U-hiPSC能够向视网膜命运分化，并形成3D视网膜类器官，其中包含分层的神经视网膜，所有视网膜细胞类型都像在体内一样位于适当的层中。更重要的是，U-hiPSC产生了具有所有亚型的高度成熟的光感受器，甚至还有富含红/绿锥细胞的光感受器。我们的数据表明，至少在视网膜类器官的环境中，向培养基中添加RA对于U-hiPSC来源的光感受器的成熟和特异性并非必要。利用U-hiPSC成功实现视网膜分化，为细胞治疗、疾病建模和药物筛选提供了诸多机会，尤其是在视网膜疾病的个性化医疗方面，因为尿液细胞可以从患者及其亲属身上无创采集。
