An Optimized System for Effective Derivation of Three-Dimensional Retinal Tissue via Wnt Signaling Regulation

Stem Cells
Ziming LuoJian Ge

Abstract

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.

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Citations

Sep 15, 2020·Frontiers in Neuroscience·Nanda BoonLucie P Pellissier
Aug 15, 2019·Tissue Engineering. Part a·Mireille M J P E SthijnsClemens A van Blitterswijk
Feb 24, 2019·Stem Cell Research & Therapy·Mingjun TangJian Ge
Dec 5, 2019·Genes·Peter M J Quinn, Jan Wijnholds
May 12, 2020·Tissue Engineering and Regenerative Medicine·Sanaz BehtajMaksym Rybachuk
Nov 3, 2020·Frontiers in Cellular Neuroscience·Ratnesh K Singh, Igor O Nasonkin
Apr 6, 2021·Molecular Therapy. Methods & Clinical Development·Julia OswaldPetr Baranov

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