Transplantation of retinal progenitor cells from optic cup-like structures differentiated from human embryonic stem cells in vitro and in vivo generation of retinal ganglion-like cells.

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Transplantation of retinal progenitor cells from optic cup-like structures differentiated from human embryonic stem cells in vitro and in vivo generation of retinal ganglion-like cells.

Stem Cells Dev. 2018 Dec 10;:

Authors: Wang S, Chen L, Zhang P, Wang X, Sun Y, Ma L, Liu Q, Zhou G

Abstract
Human embryonic stem cells (hESCs) have the potential to differentiate along the retinal lineage. We have efficiently differentiated human pluripotent stem cells (hPSCs) into optic cup-like structures by using a novel retinal differentiation medium (RDM).The purpose of this study was to determine whether the retinal progenitor cells (RPCs) derived from hESCs can integrate into the host retina and differentiate into retinal ganglion cells (RGCs) in vivo. In the present study, hESCs (H9-GFP) were induced to differentiate into optic cup-like structures by using our novel differentiation system. The RPCs extracted from the optic cup-like structures were transplanted into the vitreous cavity of N-Methyl-D-aspartic acid (NMDA)-treated mice. Sham-treated eyes received the same amount of retinal differentiation medium (RDM). The host retinas were analyzed by triple immunofluorescence on the 4th and 5th weeks after transplantation. The optic cup-like structures were efficiently differentiated from hESCs by using our novel differentiation system in vitro for 6-8 weeks. The RPCs extracted from the optic cup-like structures migrated and integrated into the GCL of the host retina. Furthermore, the remaining transplanted cells were spread over the GCL and had a complementary distribution with host residual RGCs in the GCL of the mouse retina. Surprisingly, some of the transplanted cells expressed the RGC-specific marker Brn3a. These findings demonstrated that the RPCs derived from hESCs could integrate into the host GCL and differentiate into retinal ganglion-like cells in vivo, suggesting that RPCs can be used as an ideal source in supplying countless RGC and ESC-based replacement therapies may be a promising treatment to restore vision in patients with degenerative retinal diseases.

PMID: 30526386 [PubMed - as supplied by publisher]

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