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Editors Selection IGR 15-4
Basic Science: Stem cells
Comment by Keith Martin & Tasneem Khatib on:
69145 Stage-specific differentiation of iPSCs toward retinal ganglion cell lineage, Deng F; Chen M; Liu Y et al., Molecular Vision, 2016; 22: 536-547
Induced pluriplotent stem cells (iPSCs) are a focus of much current interest in regenerative medicine. iPSCs are derived from differentiated cells that are reprogrammed for autologous transplantation as a cell replacement strategy, giving potential benefits over other stem cell strategies in terms of ethical considerations and immune rejection.
In this study, Deng and co-workers described a regime to produce retinal precursors (RPCs) capable of differentiating into retinal ganglion cells (RGCs) from human iPSCs derived from human Tenon's capsule fibroblasts (TiPSCs).
The authors reported an upregulation of eye field transcription factors in DKK1, Noggin and Lefty A (DNL) treated cells relative to controls with 23.14% of all cells immunopositive for the RGC-specific marker Brn3b following additional Atoh7 overexpression. The discrepancy between 80% transfection efficiency of RPCs using the Atoh7 plasmid and 23.14% Brn3b immunopositive cells was noted by the authors and may indicate a need for other factors to optimize RGC differentiation from RPCs.
It was of interest that TiPSCs adopted neuro-ectodermal characteristics in the absence of exogenous stimuli. A control group with Atoh overexpression in RPCs that had not been treated with DNL might have helped the clarify contribution this regimen provides to RGC differentiation. Also, the relationship between Ca2+ influx and synaptophysin immunofluorescence could perhaps have been strengthened with the demonstration of co-localization with RGC-specific markers.
Despite these reservations, this study adds support to the possible use of human iPSCs as an RGC replacement strategy by demonstrating the potential for functional RGC differentiation in vitro. The use of human Tenon's fibroblasts is of particular interest in the context of glaucoma patients due to the ease of access during glaucoma surgery. The need for in-vivo studies remains, optimizing the control of differentiation to minimize tumor formation, integration into the host retinal architecture, axon projection and synapse formation at distant and appropriate targets in the brain.
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