The apple of a bioengineer’s eye: mature photoreceptors

by Angela C.H. McDonald

Last spring, I wrote about the remarkable generation of self-organizing retinal tissue created from mouse embryonic stem cells. The study successfully created all major retinal components including photoreceptors, albeit at a low abundance. However, while multi-layered optic tissue did form, the alignment and organization of mature retinal cell types differed from that of the mouse eye in vivo.

The missing ingredient in this experiment was a physical, instructive cue to direct retinal cells into the complex structural pattern of the eye. 

A recent paper published in Biomaterials by another group of researchers described a biomaterials-based approach for creating organized photoreceptor cells from human embryonic stem cells.

Human embryonic stem cells were differentiated into retinal cells and seeded onto a specially designed scaffold positioned on top of a retinal pigment epithelial cell layer. This resulted in the organization of cells into a complex retinal architecture.

The scaffold used in this study was designed with eye development in mind, containing long, narrow, highly packed cylindrical microchannels with spatial dimensions representative of progenitor cell organization in vivo. By mimicking columnar units present in the retina, the stem cell-derived photoreceptors organized into a complex, multi-layered pattern as instructed by the physical constraints imposed by the scaffold.

Retinal maturation characteristics such as the layer separation of photoreceptors and interneurons as well as advanced photoreceptor morphology suggest that these cells may have improved functional properties in vivo, however this was not tested.

While far from the clinic, the correct anatomical orientation of retinal cells directed by this scaffold is exciting. 

Many preclinical studies will have to be performed using this system, beginning with transplantation studies in rodent models. Previous transplantation studies of single human pluripotent stem cell-derived retinal cells have shown limited functional improvement but perhaps the transplantation of organized retinal cells in a scaffold will prove to be more fruitful.

While only an in vitro study, these researchers kept clinical translatability in mind and created their scaffold out of an FDA-approved polymer. The polymer called poly (lactic-co-glycolic acid) or PGLA is highly biocompatible and is biodegradable. Within the body, PGLA will degrade into single molecules of glycolic and lactic acid that can subsequently be metabolized by retinal pigment epithelium.

It seems that bioengineers and materials scientists will play an increasingly important role in stem cell therapy efforts by creating tools that provide physical and mechanical cues driving the organization and function of mature cells.