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

Abstract

Purpose : Optic neuropathy, also known as retinal ganglion cell (RGC) degeneration, is one of the leading causes of vision loss. 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 aimed to evaluate the effects of serial novel biomimetic polybenzyl glutamate (PBG) scaffolds on culturing iPSC-derived RGC progenitors.

Methods : The present study was designed to evaluate the effects of serial novel biomimetic polybenzyl glutamate (PBG) scaffolds with directional guidance on culturing iPSC-derived RGC progenitors. The materials used to prepare the scaffold was poly (γ-benzyl-L-glutamate) (PBG) and its derivatives, poly (γ-benzyl-L-glutamate)-r-poly(L-glutamic acid) (PBGA20) and the sodium salt of poly (γ-benzyl-L-glutamate)-r-poly (L-glutamic acid) (PBGA20-Na).

Results : 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. Cells of the PBG group were differentiated toward retinal lineage that the differentially expressed genes were mainly associated with neuronal differentiation, neuronal maturation, and more specfically, retinal differentiation and maturation. Through modification of the materials, we found that the polyelectrolyte, PBGA20-Na with extraordinary electrical activity showed a significant promotion of the neuron outgrowth without adding extra biomolecules or conductive materials.

Conclusions : The novel electrospinning PBG scaffold is benficial 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. Among the groups, our data revealed that PBGA20-Na may be the most potential material for bioengineering cell therapy. The novel culture system may be helpful in future disease modeling, pharmacological screening, autologous transplantation, as well as narrowing the gap to clinical application.

This is a 2020 ARVO Annual Meeting abstract.