An Ex Vivo Eye Facsimile System (EVES) to evaluate transplantation strategies for cell replacement therapy

Abstract

Purpose : Promising cell replacement therapies have transplanted a variety of stem-like cells (STLC) into the sub-retinal space (SRS) with mixed success. However, behaviors of transplanted STLCs able to promote synaptic communication within adult retinal tissue remain incompletely understood. Our group has recently illustrated that combinatory electric and chemical fields increased STLC migration distance, in vitro, by over three times that seen in either field, individually. Our current work develops an ex vivo eye facsimile system (EVES) to evaluate how different electric and chemotactic fields (EC) can drive the migration and integration of STLCs transplanted into the host eye.

Methods : The device is comprised of 4 parts, either microfabricated or 3D printed, as shown (Fig. 1A). A Chemical Reservoir to drive concentration gradient fields, a Cathode Chamber and an Anode Chamber to apply external electric fields, and a Media Reservoir to refresh media in fluidic contact with the mimic/explant to promote viability. Late-stage photoreceptor progenitors were used as STLCs transplanted into eye mimics/explants using external fields of the EVES. The mimics/explants were then sectioned and imaged to determine STLC penetration depth and interaction with host tissue (Fig. 1B).

Results : Initial studies used the EVES to illustrate dramatic differences in penetration depth of STLCs when using EC stimuli and alginate beads to facsimile rodent eyes. As seen (Fig. 1C), EC directed STLC migration within 250mm depths of eye facsimiles in contrast to the 20mm distances measured in control. STLCs remained viable for several days in the EVES and penetrated eye facsimiles as a function of stimulus duration and application.

Conclusions : Our robust EVES system provides a quantitative and experimental testing model able to evaluate contemporary transplantation strategies, including use different STLCs for cell replacement therapy as well as in vivo procedures of sub-retinal injection and STLC insertion with and without the retinal pigment epithelium.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure 1: Description of EVES. (A) Images of the 4 separate components and their assembly. (B) Enlarged schematic of the whole-eye explant and transplantable STLCs upon anode surface. (C) Measured penetration depth of STLCs within eye facsimile using EVES to apply external electric and chemical fields for migration.