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Open AccessArticle

Polybenzyl Glutamate Biocompatible Scaffold Promotes the Efficiency of Retinal Differentiation toward Retinal Ganglion Cell Lineage from Human-Induced Pluripotent Stem Cells

1
Department of Ophthalmology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan
2
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan
3
Molecular Imaging Center, National Taiwan University, Taipei 10617, Taiwan
4
Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 10002, Taiwan
5
Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA
6
Boston VA Healthcare System, Boston, MA 02130, USA
7
Institute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan
8
Geriatric Research Education and Clinical Center, Office of Research and Development, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA 01730, USA
9
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei 10002, Taiwan
10
Department of Materials Science and Engineering, National Taiwan University, Taipei 10617, Taiwan
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(1), 178; https://doi.org/10.3390/ijms20010178
Received: 24 October 2018 / Revised: 27 December 2018 / Accepted: 29 December 2018 / Published: 5 January 2019
(This article belongs to the Special Issue Cell-Biomaterial Interaction)
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. View Full-Text
Keywords: induced pluripotent stem cells; retinal ganglion cells; optic neuropathy; glaucoma; polybenzyl glutamate; electrospinning scaffold; tissue engineering induced pluripotent stem cells; retinal ganglion cells; optic neuropathy; glaucoma; polybenzyl glutamate; electrospinning scaffold; tissue engineering
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Chen, T.-C.; She, P.-Y.; Chen, D.F.; Lu, J.-H.; Yang, C.-H.; Huang, D.-S.; Chen, P.-Y.; Lu, C.-Y.; Cho, K.-S.; Chen, H.-F.; Su, W.-F. Polybenzyl Glutamate Biocompatible Scaffold Promotes the Efficiency of Retinal Differentiation toward Retinal Ganglion Cell Lineage from Human-Induced Pluripotent Stem Cells. Int. J. Mol. Sci. 2019, 20, 178.

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