Polybenzyl glutamate biocompatible scaffold promotes the efficiency of retinal differentiation toward retinal ganglion cell lineage from human-induced pluripotent stem cells
Journal
International Journal of Molecular Sciences
Journal Volume
20
Journal Issue
1
Pages
178
Date Issued
2019
Author(s)
She P.-Y.
Chen D.F.
Lu J.-H.
Huang D.-S.
Chen P.-Y.
Lu C.-Y.
Cho K.-S.
Chen H.-F.
Su W.-F.
Abstract
Optic neuropathy is one of the leading causes of irreversible blindness caused by retinal ganglion cell (RGC) degeneration. The development of induced pluripotent stem cell (iPSC)-based therapy opens a therapeutic window for RGC degeneration, and tissue engineering may further promote the efficiency of differentiation process of iPSCs. The present study was designed to evaluate the effects of a novel biomimetic polybenzyl glutamate (PBG) scaffold on culturing iPSC-derived RGC progenitors. The iPSC-derived neural spheres cultured on PBG scaffold increased the differentiated retinal neurons and promoted the neurite outgrowth in the RGC progenitor layer. Additionally, iPSCs cultured on PBG scaffold formed the organoid-like structures compared to that of iPSCs cultured on cover glass within the same culture period. With RNA-seq, we found that cells of the PBG group were differentiated toward retinal lineage and may be related to the glutamate signaling pathway. Further ontological analysis and the gene network analysis showed that the differentially expressed genes between cells of the PBG group and the control group were mainly associated with neuronal differentiation, neuronal maturation, and more specifically, retinal differentiation and maturation. The novel electrospinning PBG scaffold is beneficial for culturing iPSC-derived RGC progenitors as well as retinal organoids. Cells cultured on PBG scaffold differentiate effectively and shorten the process of RGC differentiation compared to that of cells cultured on coverslip. The new culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Subjects
Electrospinning scaffold; Glaucoma; Induced pluripotent stem cells; Optic neuropathy; Polybenzyl glutamate; Retinal ganglion cells; Tissue engineering
SDGs
Other Subjects
biomimetic material; polybenzyl glutamate; unclassified drug; biomaterial; glutamic acid; peptide; transcriptome; Article; autotransplantation; blindness; cell degeneration; cell lineage; cell maturation; cell proliferation; controlled study; electrospinning; gene expression; human; human cell; immunofluorescence; immunohistochemistry; induced pluripotent stem cell; nerve cell differentiation; optic nerve disease; real time polymerase chain reaction; retina ganglion cell; RNA sequence; scanning electron microscopy; tissue engineering; animal; axon; cell culture; cell differentiation; chemistry; cytology; drug effect; gene regulatory network; genetics; induced pluripotent stem cell; metabolism; mouse; retina ganglion cell; sequence analysis; signal transduction; tissue scaffold; ultrastructure; Animals; Axons; Biocompatible Materials; Cell Differentiation; Cell Lineage; Cells, Cultured; Gene Regulatory Networks; Glutamic Acid; Humans; Induced Pluripotent Stem Cells; Mice; Peptides; Retinal Ganglion Cells; Sequence Analysis, RNA; Signal Transduction; Tissue Scaffolds; Transcriptome
Publisher
MDPI AG
Type
journal article