# Multipotent ABCB5-positive cell therapeutics for corneal disease

> **NIH NIH R24** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $1,176,331

## Abstract

PROJECT SUMMARY
The limbus contains a small subpopulation of rare limbal stem cells (LSC) that continually repopulates the
corneal epithelium. Patients with limbal stem cell deficiency (LSCD) are unable to regenerate the corneal
epithelium, resulting in "conjunctivalization" of the corneal stroma that triggers neovascularization, chronic
inflammation, and ultimately blindness due to an irreversibly opaque cornea. Several approaches have
been used to replace LSC by transplanting limbal tissue or ex vivo expanded limbal cells. These procedures
have obtained some success, mainly using autologous limbal tissue from patients with unilateral LSCD.
However, these treatments remain technically challenging. Moreover, the larger population of patients with
bilateral LSCD has no source of autologous LSC and much less success was observed with allogeneic
limbal tissue transplants, indicating new approaches are needed for successful treatment of bilateral LSCD
patients. Our collaborative research group has now discovered two new sources of purified donor ABCB5+
stem cells for patients with bilateral LSCD (i) allogeneic immunosuppressive ABCB5+ LSC, and (ii)
autologous multipotent dermal-skin-derived ABCB5+ DSC (Dermal Stem Cells). We recently discovered
that the ABCB5 gene, a new member of the ATP-binding cassette (ABC) superfamily of active transporters,
identifies multipotent stem cells in the limbus (LSC) and the skin (DSC) in mice and humans. Importantly,
ABCB5 is a cell surface protein and specific monoclonal antibodies developed by our laboratories are
capable of prospectively isolating pure ABCB5-positive stem cells from the limbus and skin. Recently
published proof-of-principle experiments demonstrated that purified human ABCB5+ (but not ABCB5
negative) LSC were capable of long-term restoration of the corneal epithelium in an immunodeficient mouse
model of LSCD, indicating that this purified LSC population has the potential to significantly improve therapy
for corneal disease associated with LSCD. The goal of the current grant application is to translate our
laboratory research findings into new ABCB5+ stem cell-based therapies to treat unilateral and bilateral
LSCD patients. Our overall hypothesis is that ABCB5+ stem cells from the limbus or skin can be isolated
and expanded in vitro as a source of stem cells to regenerate the corneal epithelium when transplanted to
recipients with either a unilateral or bilateral LSCD. The three Modules of this project will: Validate the
regenerative potential of purified in vitro-expanded ABCB5+ LSC (Module 1) and purified in vitro-expanded
ABCB5+ DSC (Module 2) for unilateral and bilateral LSCD patients; and (Module 3) create an LSC Biobank
for clinical transplantation and conduct studies resulting in FDA IND approval.

## Key facts

- **NIH application ID:** 10374830
- **Project number:** 5R24EY028767-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** NATASHA Y FRANK
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,176,331
- **Award type:** 5
- **Project period:** 2018-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374830

## Citation

> US National Institutes of Health, RePORTER application 10374830, Multipotent ABCB5-positive cell therapeutics for corneal disease (5R24EY028767-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10374830. Licensed CC0.

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