# Live Imaging of Intact Airway

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $557,684

## Abstract

The integrity of the lining of the airways relies on multiple functions of its epithelial stem cells.
We hypothesize that the airway stem cell behavior is regulated by the cells and the forces that
surrounds them, including other epithelial cells, subepithelial mesenchymal cells, and external
mechanical forces exerted on the epithelium. How these varied components regulate the
behavior of airway progenitor cells is largely unknown. Furthermore, basal stem cell – niche
interactions may explain the increasingly recognized heterogeneity within this progenitor cell
population, including regional and tissue-level heterogeneity in basal stem cell behavior.
Although progenitor cell – niche interactions have been described with live imaging in other
systems, the constant motion and challenging access of the respiratory system has hampered
the development of platforms for live imaging of the airways at high resolution.
We combined emerging stem cell biology and live imaging technologies to develop a novel
airway explant live imaging platform. We imaged the maintenance and regeneration of the
airway epithelium in a mouse airway explant, surrounded by all of the major components of its
3D multicomponent microenvironment, including the ECM and the mesenchyme. We present
preliminary data on tracking individual stem cells during regeneration with two photon laser
scanning microscopy, including visualization of stem cell differentiation with fluorescent
reporters and analysis of ciliated cell function with novel video-rate imaging modalities. To
define the airway stem cell microenvironment and to test its role in progenitor cells function, we
visualize and putative cellular niche components and test their role by laser and toxin-mediated
ablation. We propose to use cellular engraftment followed by application of mechanical forces to
check the role of the microenvironment in establishing planar polarity, and to study the
relationship of proliferation, migration and differentiation in collective cell migration in the airway
epithelium.

## Key facts

- **NIH application ID:** 9999031
- **Project number:** 5R01HL142559-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Charles P. Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $557,684
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999031

## Citation

> US National Institutes of Health, RePORTER application 9999031, Live Imaging of Intact Airway (5R01HL142559-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999031. Licensed CC0.

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