NIH Reporter #1R01EY038193-01A1

Structurally Programmed Microfluidic Bioreactors to Manufacture Retinal Organoids for Regenerative Medicine

Award to University of California-Irvine to develop a semi-automated bioreactor system for manufacturing retinal organoids, aiming to improve production quality and therapeutic testing in a rat model of retinitis pigmentosa.

Description

This project aims to engineer a semi-automated, contactless bioreactor system to improve the production of retinal organoids (ROs). These organoids are essential tools for studying retinal development, modeling diseases, and developing therapies. The goal is to develop a fully enclosed, contactless bioreactor system for consistent, high-quality manufacturing of retinal organoids, reducing labor, contamination risks, and variability. The project will initiate retinal organoids from human pluripotent stem cells, optimize cell aggregation, aggregate isolation, organoid development, and long-term maintenance. Performance will be assessed through non-invasive metabolic imaging and single-cell RNA sequencing. Additionally, the bioreactor-cultured organoids will be transplanted into a rat model of retinitis pigmentosa to evaluate therapeutic efficacy via visual function tests, OCT imaging, and histological analysis. A key innovation is the use of a photoreceptor-specific secretable reporter as a serum biomarker to monitor photoreceptor survival and integration in real time, providing a minimally invasive method to assess therapeutic outcomes. If successful, this project will deliver a scalable, low-cost, semi-autonomous platform that improves reproducibility and quality of retinal organoid production, with broad implications for regenerative medicine and basic science.

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