# Regeneration of human RPE cells from autologous urine-derived iPS cells

> **NIH NIH R21** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $232,500

## Abstract

PROJECT SUMMARY
Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the
US, and restoring retinal function in AMD patients remains a big challenge. Retinal pigment epithelium (RPE)
degeneration is the hallmark of advanced “dry” or non-neovascular AMD with no treatment available. The
implanted retinal pigment epithelial cells (RPEs) or a patch of RPE, generated from induced pluripotent stem
cells (iPSCs), provide great potential in the treatment of AMD. Autologous iPSCs possess therapeutic potential
with less immunogenicity and have less ethical controversy than human embryonic stem cells-based therapies.
Two phases are required from somatic cells to generate mature RPEs: iPSCs are reprogrammed from different
somatic cell sources located at peripheral blood, skin, or other epithelial tissues, and then iPSCs are guided to
differentiate to functional RPEs (RPEsiPSC). Despite current progress in generating RPEs from somatic cells,
several barriers remain in their clinical application, and there is an urgent need to develop an optimized
strategy with higher efficiency and rapid differentiation kinetics in the generation of RPEsiPSC. Human primary
USCs, as renal progenitors first discovered by the PI’s team, are easily accessible and possess robust cell
proliferation and renewal capacity for tissue regeneration. Our previous studies demonstrated that iPSCs
reprogrammed from USC (u-iPSCs) more efficiently and rapidly than iPSC from other cell sources. u-iPSC
efficiently differentiated into neurocytes, but RPEsu-iPSC have not been developed yet. The long-term goal of
this proposal is to use RPEs generated from autologous USC-derived iPSCs (RPEsu-iPSC) to reestablish the
interaction with photo‑receptors and prevent degeneration of the retina, restoring the vision function for
patients with AMD. The overall objective of this R21 study is to generate pure RPEs from u-iPSC (RPEsu-iPSC).
Our central hypothesis is that u-iPSC reprogrammed from USC (epithelial progentior cells) are more efficiently
and rapidly differentiated into mature RPEs (epithelalial lineage cell) with specific makers and durable tight
junction, compared to iPSC from mesenchymal cell lineages (i.e, skin fibroblasts and blood mononuclear cells).
Thus, the specific aim of this study is to develop and optimize a strategy for generating reliably archived human
RPEsu-iPSC. We will determine the efficiency of RPE differentiation from u-iPSCs and assess the function of
RPEsu-iPSC compared to that of iPSC from skin and blood cells, with adult human primary RPE as a control. We
expect that USC obtained non-invasively from AMD patients could be an optimal cell source for generating
mature RPEsu-iPSC in a cost-effective manner for personalized medicine in the treatment of AMD. This in vitro
differentiated human RPEsu-iPSC will be highly valuable and pave the ground for a future R01 proposal on an in
vivo study with autologous RPEsu-iPSC. The broader im...

## Key facts

- **NIH application ID:** 10790973
- **Project number:** 1R21EY035833-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** YUANYUAN no ZHANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $232,500
- **Award type:** 1
- **Project period:** 2024-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10790973

## Citation

> US National Institutes of Health, RePORTER application 10790973, Regeneration of human RPE cells from autologous urine-derived iPS cells (1R21EY035833-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10790973. Licensed CC0.

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