An Optimized System for Effective Derivation of Three-Dimensional Retinal Tissue via Wnt Signaling Regulation
An Optimized System for Effective Derivation of Three-Dimensional Retinal Tissue via Wnt Signaling Regulation
复制标题
通过 Wnt 信号调节有效衍生三维视网膜组织的优化系统
DOI：
10.1002/stem.2890
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发表时间：
2018-11-01
期刊：
影响因子：
5.2
通讯作者：
Ge，Jian
中科院分区：
文献类型：
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作者：
Luo，Ziming;Zhong，Xiufeng;Ge，Jian
从人诱导的多能干细胞(HiPSCs)中有效地获得三维(3D)视网膜组织可以为药物筛选提供模型，并促进针对患者的视网膜细胞替代治疗。然而，一些HiPSC系不能进行三维自组织，分化效率不高，无法满足临床需要。在这项研究中，我们开发了一个优化的3D视网膜组织派生系统。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前体细胞不能自组织的现象。通过评估DKK-1的表达并在必要时补充DKK-1，从三种常见的启动细胞类型重新编程的六个HiPSC株中区分出视网膜类器官。从优化的系统中获得的视网膜组织组织结构良好，能够存活并进一步成熟。因此，使用该系统，我们可以高效地从不同的HiPSC系中产生视网膜组织。这一新的系统在再生治疗和精确医学中有许多潜在的应用。
AbstractEffective 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.