The role of PGS/PCL scaffolds in promoting differentiation of human embryonic stem cells into retinal ganglion cells.

The stem cell-based retinal ganglion cells (RGCs) replacement therapy offers a potential to restore vision in progressive optic neuropathies including glaucoma by replacing degenerated RGCs and by simulating axonal regeneration. Injured optic nerve axons do not regenerate owing to the limited intrinsic capacity of the neurons and the inhibitory environment at the injury site. Polymeric tissue scaffolds are able to modulate the physical environment while providing structural support for transplanted cells, however, their application specific to the RGC generation has been far from conclusive. The successful generation of clinically safe and functional RGCs that can appropriately integrate into the hosts' retinas still remain largely unresolved. Our study reports on a process that enables generation of RGCs from human embryonic stem cells (hESCs) that is simple, straightforward and repeatable and, investigates the influence of the aligned poly(glycerol sebacate) (PGS)/poly(ε-caprolactone) (PCL) scaffold on this differentiation process. Our findings demonstrate that PGS/PCL scaffold promotes differentiation of hESCs into RGC-like cells possibly by the simulation of cell active environmental signalling and, facilitates the growth of RGCs neurites along their lengths. STATEMENT OF SIGNIFICANCE: Glaucoma can lead to the degeneration of retinal ganglion cells (RGCs), with consequential vision loss. RGCs are incapable of self-renewal, replacement of diseased RGCs with healthy cells has been a goal to restore vision in glaucoma patients. In this regard, stem cell RGC replacement therapy has been shown to improve vision in animal models of glaucoma, which could be facilitated by using tissue-engineered polymeric scaffolds. In this study, we generated homogenous stem cell-derived RGCs via a straightforward differentiation protocol and evaluated the effects of PGS/PCL scaffold on RGCs differentiation and growth of RGCs neurites. Our study contributes to the knowledge on how biomaterial scaffolds are able to support the regeneration of RGC neurites (i.e., axons or dendrites) as a part of a possible future clinical therapy for the treatment of glaucoma.