# Development of cell-free approaches to the treatment of limbal stem cell deficiency

> **NIH NIH R00** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $231,858

## Abstract

PROJECT SUMMARY (See instructions): 
Limbal stem cells (LSCs) give rise to the entire corneal epithelium and are known to reside in the border area
between the cornea and conjunctiva called limbus. Loss of LSCs or destruction of the LSC niche can result in Limbal
Stem Cell Deficiency (LSCD) – a common cause of vision loss in the world. While transplantation of the autologous
limbal tissues removed from the contralateral eye can cure patients with unilateral LSCD, bilateral LSCD patients
have no autologous limbal tissues available. These patients often require transplantation of allogeneic donor limbal
grafts; however, their success is highly variable. Moreover, the worldwide corneal donor shortage poses significant
challenges for the availability of allogeneic LSCs for the treatment of bilateral LSCD patients. Thus, the overarching
goal of this project is to develop cell-free LSCD therapies through the discovery of novel mechanisms of LSC
maintenance and regeneration. Our lab has discovered an ATP-binding cassette (ABC) superfamily member B5
(ABCB5) as a novel LSC marker. ABCB5-positive LSCs isolated from human donors were capable of the long-term
corneal restoration in pre-clinical LSCD models. Clinical trials are currently on the way to address the therapeutic
potential of this stem cell population in human patients. Our most recent studies aimed to explore the cellular
hierarchy within ABCB5-positive LSCs using single-cell RNA-sequencing revealed a novel LSC subpopulation that
could be differentiated from the other LSC clusters by low expression levels of the cornea-specific genes. Here we
hypothesized that this subpopulation possesses the most primitive stem cell characteristics with the highest
regenerative potential. Further in-depth analyses revealed that these cells preferentially expressed the molecules
involved in FGF, BMP, and AXL signaling cascades. We posit that these molecular pathways are essential for the
maintenance of the undifferentiated LSC phenotype and can be employed for de-novo LSC induction and restoration
of the LSC niche in the setting of bilateral LSCD. The two Aims of this proposal will: mechanistically dissect the role
of FGF7, BMP2 and AXL in the LSC maintenance using murine and human genetically engineered experimental
models (Aim 1) and will test the therapeutic potential of targeting these pathways for the treatment of LSCD in
pre-clinical murine disease models (Aim 2). Successful completion of this study will further advance our
understanding of LSC development, maintenance, and regulation with significant implications for clinical translation

## Key facts

- **NIH application ID:** 10792955
- **Project number:** 5R00EY031741-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Yuzuru Sasamoto
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $231,858
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792955

## Citation

> US National Institutes of Health, RePORTER application 10792955, Development of cell-free approaches to the treatment of limbal stem cell deficiency (5R00EY031741-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10792955. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*