An improved formulation of human neural stem cells for the treatment of geographic atrophy.

PURPOSE: This study aimed to compare the neuroprotective effects of subretinally delivered human central nervous system stem cells (HuCNS-SC) and a novel, single-cell suspension formulation, Neubright (NB) in the RCS rat. METHODS: At postnatal day 21, RCS rats were subretinally injected with a 150,000 cell dose of either HuCNS-SC or NB in a 2 μL volume. The contralateral control eye was injected with balanced salt solution. Visual function outcomes were measured using optokinetic tracking and electroretinography. Whole globes were harvested at P60 and P180 for immunofluorescence (IF). To identify cells in the subretinal space, retinal cross-sections were stained with a human specific marker (STEM121). Cell spread, outer nuclear layer (ONL) thickness, and cell migration were quantified using confocal microscopy and image J. RESULTS: IF demonstrated a clear presence of STEM121-positive cells in the subretinal space after delivery of both HuCNS-SC and NB. The ONL was thicker in areas adjacent to the injected cells, whereas a greater degree of degeneration was observed outside of treated areas. The novel NB formulation had significantly increased cell spread and visual performance compared to the original HuCNS-SC formulation. CONCLUSIONS: A novel single-cell suspension of human neural stem cells, NB, with high cell viability was successfully generated. NB improved cell spread in the subretinal space compared to HuCNS-SC improving visual outcomes in the RCS rat. Translational Relevance: This bridging study will be used as an investigational new drug approval enabling study to evaluate NB in clinical trials for macular retinal degeneration.