Abstract
Purpose :
Stem cell therapies have shown great promise to restore vision in patients affected by retinal degenerative diseases. However, there are still challenges that remains due to the efficacy gap between in vitro studies and in vivo cell transplantation.
This is partly due to the hostile microenvironments in which these cells are transplanted in.
In retinitis pigmentosa (RP), the loss of vision is due to the death of both rod and cone photoreceptors. The absence of rods causes the loss of critical metabolic factors directly affecting cone survival.
To address this key issue, we have created a 3D hydrogel-based stem cell product that secretes neuroprotective factors in the vitreous to preserve cone photoreceptors. This biocompatible hydrogel mimics the in vivo extracellular matrix to offer a thriving environment for cellular proliferation and viability. Our biomaterial encapsulates a novel enriched target cell population that produces specific neurotrophic factors which are lost in RP.
Methods :
We have engineered this technology by combining material science and cell biology and have examined its effects in vitro on cone cells and in vivo with the rd-1 mice model (retinal degenerative mice). Our biomaterial is gelatin and hyaluronic acid based, creating an in-situ crosslinking hydrogel that becomes fully gel only once injected through a normal 41-gauge needle.
Our novel cell population was isolated from fetal tissue using a slow microfluidic technic to purify rod precursors cells with high purity and viability. These cells express all common rod markers and can be expanded and banked using novel cell culture techniques.
Results :
Our study shows that our technology is a multimodal therapy that targets specific neurodegenerative pathways such as neuro-glycolysis and neuro-inflammation. The neurotropic factors present can enhance glucose uptake by cone photoreceptors and reduce the expression of W6/32 markers indicating a reduction in neuro-inflammation. Following the injection of our stem cell-matrix product in the vitreous of rd-1 mice (P26) we observed a 10-fold increase in cone survival (central retina) which translated into the mice ability to perceive light.
Conclusions :
This technology is the first of its type to be gene agnostic and which can target multiple pathways that are affected in RP patients. We expect to be able to treat all patients in mid-stage RP (around 30,000) in the US.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.