An Optimized System for Effective Derivation of Three-Dimensional Retinal Tissue via Wnt Signaling Regulation
| Autor: | Xiufeng Zhong, Kang Li, Jian Ge, Chaochao Xu, Ziming Luo, Bingbing Xie, Yuchun Liu, Meifang Ye, Kaijing Li |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell type Wnt signaling pathway Cell Differentiation Retinal Cell Biology Biology Regenerative medicine Retina Cell biology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry DKK1 Humans Molecular Medicine Stem cell Progenitor cell Induced pluripotent stem cell Wnt Signaling Pathway Developmental Biology |
| Zdroj: | Stem Cells. 36:1709-1722 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.2890 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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