# Epithelial stem/progenitor cells as repair agents in diffuse alveolar damage

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $1,186,445

## Abstract

ABSTRACT
The overall goal of this application is to develop a compelling rationale and workable methodology for the
treatment of diffuse alveolar damage with transplanted human epithelial stem/progenitor cells capable of long
term engraftment and improved organ function. Stem/progenitor replacement therapy is envisioned as a
meaningful therapeutic adjunct in several clinical situations dominated by diffuse alveolar damage with
epithelial loss: severe, acute lung injury, e.g. due to influenza or other causes of ARDS, as well as acute
exacerbations of chronic fibrotic lung disease. Recent studies discussed in the application indicate effective
alveolar regeneration, and thus improved lung function, requires both a first phase of expansion and migration
of stem/progenitor cells to re-establish alveolar barriers followed by a second phase of differentiation of new
barrier cells into mature type II (AEC2s) and type I alveolar cells. To develop a translational program for
alveolar regeneration by transplantation of healthy lung epithelial stem/progenitor cells, three basic objectives
are advanced: (1) Further delineation of the signaling programs by which endogenous human distal lung
epithelial stem cells can be activated following major injury to establish new alveolar barriers and then
differentiate to AEC2s. (2) In vitro development of pools of human distal (small airway and alveolar) epithelial
stem cells, both endogenous and iPSC-derived, suitable for transplantation and directed differentiation in mice.
Distal basal-like cells from human iPS cells using gene edited cells reporting surfactant protein C, cytokeratin
17 (Krt17), and NKX2.1 will be used to develop a workable protocol for directed differentiation after transplant.
(3) Employ models of lung repair/regeneration approachable by transplantation as tools to assess the
regenerative potential of human epithelial stem/progenitor cells. Macaque iPS cells suitable for
transplantation into influenza-infected monkeys will be used as a primate model for therapy. It is anticipated
that functional improvement in gas exchange and alveolar histology can be achieved in primates, providing
both a rationale and methodology for stem/progenitor cells as adjunctive therapy after severe acute lung injury
in humans.

## Key facts

- **NIH application ID:** 10418711
- **Project number:** 5U01HL134766-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Harold A Chapman
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,186,445
- **Award type:** 5
- **Project period:** 2016-09-21 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418711

## Citation

> US National Institutes of Health, RePORTER application 10418711, Epithelial stem/progenitor cells as repair agents in diffuse alveolar damage (5U01HL134766-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10418711. Licensed CC0.

---

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