# Generation of functional lung stem cells from human iPSCs

> **NIH NIH U01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $410,909

## Abstract

From newborns to the elderly, diseases of the respiratory tract are a major cause of morbidity and mortality
in the United States. For many of these diseases, there is a desperate need for effective treatments. A
regenerative medicine approach using cell-based therapy could, in theory, drastically improve the lives of
these patients. The long term goal of this application is to address critical hurdles to the development and
application of alveolar and airway stem cells derived from induced pluripotent stem cells (iPSCs) as safe
and effective cell-based therapies for lung disease. Significant progress has been made in deriving lung
epithelial cells from human iPSCs over the past decade. Increasingly sophisticated directed differentiation
protocols have produced more mature and functional airway and alveolar epithelial cells. Despite this
progress, current protocols do not generate pure populations of cells. Knock-in fluorescent reporters have
been used to purify lung epithelial cells and confirmed their similarity to primary controls but this approach
is undesirable for cell-based therapies. There are crucial questions that must be addressed prior to the
application of these cells to human patients. What tools are required to generate pure populations of lung
stem cells and how can we best determine the safety and efficacy of those cells? In this application we
address these key questions. First we develop a panel of new tools that will be required for clinically-
relevant directed differentiation protocols through the application of cell-sorting strategies using antibodies
against cell-surface makers to purify both alveolar (CKIT/CPM) and airway (ITGA6) stem cells from a panel
of human iPSCs. These tools and protocols obviate the need for knock-in reporters, utilize serum-free
defined media, and establish standardized manufacturing approaches that will be essential for successful
IND applications of these novel cells. Next, and with support from the Regenerative Medicine Innovation
Catalyst, we perform the most in-depth characterization to date of iPSC-derived alveolar and airway stem
cells. These global proteomic, phosphoproteomic, metabolic/respiromic, transcriptomic, and genomic
datasets will provide the research community with an essential resource. Safety of these cells in terms of
genetic stability and tumorgenicity remains a major concern when considering clinical applications. We
assess the safety profile of iPSC-derived airway and alveolar stem cells over long-term in vitro culture and
in vivo. Finally, we assess the efficacy and potency of these cells. We employ established in-vitro assays to
address fundamental questions of self-renewal and multi-lineage differentiation potential compared to
primary controls and ultimately determine their capacity for engraftment in lung injury models in mice. At the
conclusion of this proposal we will have developed new tools to purify alveolar and airway stem cells from
iPSCs and will have establish...

## Key facts

- **NIH application ID:** 9951099
- **Project number:** 5U01HL148692-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Finn Hawkins
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,909
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951099

## Citation

> US National Institutes of Health, RePORTER application 9951099, Generation of functional lung stem cells from human iPSCs (5U01HL148692-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9951099. Licensed CC0.

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