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Cell replacement with stem cell-derived retinal ganglion cells from different protocols.

ABSTRACT: Glaucoma, characterized by a degenerative loss of retinal ganglion cells, is the second leading cause of blindness worldwide. There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury. Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases. In this review, we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture, including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation outcomes. Next, we discuss using 3D retinal organoids for retinal ganglion cell transplantation, comparing cell suspensions and clusters. This review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation, with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

SUBMITTER: Luo Z

PROVIDER: S-EPMC10664109 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Cell replacement with stem cell-derived retinal ganglion cells from different protocols.

Luo Ziming Z Chang Kun-Che KC

Neural regeneration research 20240401 4

Glaucoma, characterized by a degenerative loss of retinal ganglion cells, is the second leading cause of blindness worldwide. There is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after injury. Human stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative diseases. In this review, we first discuss a 2D protocol for retinal ganglion cell differentiation from ...[more]

PMID: 37843215

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Project description:Human Müller glia with stem cell characteristics (hMGSCs) have been shown to improve retinal function upon transplantation into rat models of retinal ganglion cell (RGC) depletion. However, their translational potential may depend upon successful engraftment and improvement of retinal function in experimental models with anatomical and functional features resembling those of the human eye. We investigated the effect of allogeneic transplantation of feline Müller glia with the ability to differentiate into cells expressing RGC markers, following ablation of RGCs by N-methyl-d-aspartate (NMDA). Unlike previous observations in the rat, transplantation of hMGSC-derived RGCs into the feline vitreous formed aggregates and elicited a severe inflammatory response without improving visual function. In contrast, allogeneic transplantation of feline MGSC (fMGSC)-derived RGCs into the vitrectomized eye improved the scotopic threshold response (STR) of the electroretinogram (ERG). Despite causing functional improvement, the cells did not attach onto the retina and formed aggregates on peripheral vitreous remnants, suggesting that vitreous may constitute a barrier for cell attachment onto the retina. This was confirmed by observations that cellular scaffolds of compressed collagen and enriched preparations of fMGSC-derived RGCs facilitated cell attachment. Although cells did not migrate into the RGC layer or the optic nerve, they significantly improved the STR and the photopic negative response of the ERG, indicative of increased RGC function. These results suggest that MGSCs have a neuroprotective ability that promotes partial recovery of impaired RGC function and indicate that cell attachment onto the retina may be necessary for transplanted cells to confer neuroprotection to the retina. Significance: Müller glia with stem cell characteristics are present in the adult human retina, but they do not have regenerative ability. These cells, however, have potential for development of cell therapies to treat retinal disease. Using a feline model of retinal ganglion cell (RGC) depletion, cell grafting methods to improve RGC function have been developed. Using cellular scaffolds, allogeneic transplantation of Müller glia-derived RGC promoted cell attachment onto the retina and enhanced retinal function, as judged by improvement of the photopic negative and scotopic threshold responses of the electroretinogram. The results suggest that the improvement of RGC function observed may be ascribed to the neuroprotective ability of these cells and indicate that attachment of the transplanted cells onto the retina is required to promote effective neuroprotection.

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Cell replacement with stem cell-derived retinal ganglion cells from different protocols.

Publications

Cell replacement with stem cell-derived retinal ganglion cells from different protocols.

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