State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Stem Cells. 2018 Nov;36(11):1709-1722. doi: 10.1002/stem.2890. Epub 2018 Sep 8.
Effective derivation of three-dimensional (3D) retinal tissue from human-induced pluripotent stem cells (hiPSCs) could provide models for drug screening and facilitate patient-specific retinal cell replacement therapy. However, some hiPSC lines cannot undergo 3D self-organization and show inadequate differentiation efficiency to meet clinical demand. In this study, we developed an optimized system for derivation of 3D retinal tissue. We found that the Wnt signaling pathway antagonist Dickkopf-related protein 1 (DKK-1) rescued the inability of differentiated retinal progenitors to self-organize. By evaluating DKK-1 expression and supplying DKK-1 if necessary, retinal organoids were differentiated from six hiPSC lines, which were reprogramed from three common initiating cell types. Retinal tissues derived from the optimized system were well organized and capable of surviving for further maturation. Thus, using this system, we generated retinal tissues from various hiPSC lines with high efficiency. This novel system has many potential applications in regenerative therapy and precision medicine. Stem Cells 2018;36:1709-1722.
有效的三维（3D）视网膜组织从人类诱导多能干细胞（hiPSCs）可以提供药物筛选模型，并促进特定患者的视网膜细胞替代治疗。然而，一些 hiPSC 系不能进行 3D 自我组织，并且分化效率不足以满足临床需求。在本研究中，我们开发了一种优化的 3D 视网膜组织衍生系统。我们发现 Wnt 信号通路拮抗剂 Dickkopf 相关蛋白 1（DKK-1）挽救了分化的视网膜祖细胞不能自我组织的能力。通过评估 DKK-1 的表达并在必要时提供 DKK-1，从三个常见起始细胞类型重新编程的六个 hiPSC 系分化出了视网膜类器官。从优化系统中衍生的视网膜组织排列整齐，能够存活以进一步成熟。因此，使用该系统，我们从各种 hiPSC 系中高效地生成了视网膜组织。这个新系统在再生治疗和精准医学中有许多潜在的应用。干细胞 2018;36:1709-1722.
