# Activation of Wnt signaling to improve in vitro human limbal stem cell maintenance

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $17,541

## Abstract

PROJECT SUMMARY
Limbal epithelial stem/progenitor cells (LSCs) in the human corneal epithelium are the front line
of defense to maintain transparency of the cornea. Loss or dysfunction of the LSCs leads to
limbal stem cell deficiency (LSCD), which causes pain, inflammation, and loss of corneal
transparency in patients. Cultivated LSCs from a patient’s healthy LSCs can be transplanted into
the diseased cornea to replenish the LSCs, but maintaining sufficient LSCs and preventing LSC
differentiation in culture to allow for a successful transplant remain a major challenge in the
field. A canonical Wnt mimic small molecule and the expression of the Wnt co-receptor and
putative LSC marker Fzd7 have separately been shown to improve the cultivation of LSCs while
preventing differentiation. The goal of this proposal is to use a novel hybrid small molecule,
termed Fzd7-ND, that specifically binds Fzd7 and the Wnt co-receptor LRP5/6, to activate
canonical Wnt signaling. The kinetics of Fzd7-ND of Wnt activation will be investigated using a
TopFlash assay first. The function and population of cultivated LSCs following Fzd7-ND
treatment will be evaluated as described using biomarkers in the parent grant. The proposed
project will inform further development of Wnt mimic small molecule Fzd7-ND to maximize the
population of undifferentiated LSCs in culture. The knowledge gained from the proposed project
will allow continued improvement of patient-specific LSCD treatment.

## Key facts

- **NIH application ID:** 10621625
- **Project number:** 3R01EY021797-09S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Sophie Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $17,541
- **Award type:** 3
- **Project period:** 2012-09-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10621625

## Citation

> US National Institutes of Health, RePORTER application 10621625, Activation of Wnt signaling to improve in vitro human limbal stem cell maintenance (3R01EY021797-09S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10621625. Licensed CC0.

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