# Transplantation of Adult, Tissue-Specific RPE Stem Cells as Therapy for Non-exudative Age-Related Macular Degeneration AMD

> **NIH NIH U01** · REGENERATIVE RESEARCH FOUNDATION · 2020 · $326,250

## Abstract

Summary
The goal of this project is to develop a cell-based therapy as a durable sub-retinal transplant to benefit patients
with dry age-related macular degeneration (AMD). We recently discovered a novel adult retinal pigment
epithelial stem cell, the RPESC, in the human RPE layer that self-renews and produces highly pure
populations of RPE progeny (RPESC-RPE). In collaboration with NEI researchers, we have shown that
RPESC-RPE recapitulate key functions of native RPE, including polarized cytokine secretion, fluid transport
and phagocytosis of rod outer segments, critical for photoreceptor cell survival and retinal health. With the U.
Rochester GMP facility (USCGF), we have developed a robust, reproducible cGMP manufacturing process.
Each RPESC line is isolated from donated globes using material that would otherwise be discarded after
cornea collection. There is no shortage of starting material as c.100,000 globes/year are donated to US eye
banks with CLIA-certified FDA-compliant donor testing. RPESCs isolated from a single donor can produce
5x108 RPESC-RPE progeny after only 2 passages. The RPESC-RPE product is simple to manufacture, and
the low-cost to produce multiple master cell banks (MCBs) makes HLA matching to patients feasible in the
future. Following FDA guidance, we have produced a clinical grade MCB and performed pre-clinical IND-
enabling studies that indicate a favorable safety profile with no tumor detection or toxicity reported. Using two
different rat models, we demonstrated long-term engraftment into the RPE layer and significant vision rescue in
the Royal College of Surgeons (RCS) rat, a model previously validated for cell transplant IND-enabling studies
for AMD. We found that subretinal transplantation of adult RPESC-derived RPE at an intermediate stage of
differentiation increases vision rescue in the RCS rat, while earlier or later stage cells were significantly less
efficacious. Our studies of this efficacious stage have enabled identification of candidate potency markers. The
goals of this Regenerative Medicine Innovation Project (RMIP) Investigator-initiated RFA-HL-18-030
application are to: 1. Advance CMC for the RPESC-RPE cell product in collaboration with the RM Innovation
catalyst in anticipation of clinical trial and RMAT application; 2. Complete ongoing histology studies that
address transplanted cell function and integration and persistence in vivo, and 3. Complete and submit the IND
application and prepare for a Phase I/IIa phase clinical trial. Much progress has been made to complete each
of these aims, including IND-enabling safety and efficacy studies, which makes the proposed timeline and
budget feasible. The proposed clinical trial to transplant RPESC-RPE subretinally as a suspension uses
established vitreoretinal surgical techniques to minimize retinotomy size and surgical complications. Clinical
trial teams at the University of Michigan Kellogg Eye Center and the Stanford University Byers Eye Institute
inclu...

## Key facts

- **NIH application ID:** 9967084
- **Project number:** 5U01EY030581-02
- **Recipient organization:** REGENERATIVE RESEARCH FOUNDATION
- **Principal Investigator:** Jeffrey H Stern
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $326,250
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967084

## Citation

> US National Institutes of Health, RePORTER application 9967084, Transplantation of Adult, Tissue-Specific RPE Stem Cells as Therapy for Non-exudative Age-Related Macular Degeneration AMD (5U01EY030581-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9967084. Licensed CC0.

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