# The Role of Macrophages in Pulmonary Regeneration using a Bioengineered Whole Lung Tissue Model

> **NIH NIH F32** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $67,174

## Abstract

PROJECT SUMMARY/ABSTRACT
Fibrotic lung remodeling is a hallmark of many lung diseases, including severe influenza infection, idiopathic
pulmonary fibrosis, and COVID-19. While a basal-like epithelial cell has been identified as a central player to this
aberrant repair response, little has been done to investigate the behavior and interactions of other cells in the
diseased tissue, particularly alveolar macrophages. Therefore, the goal of this study is to leverage a biomimetic
engineered lung model system to investigate the relationship between regenerating basal-like progenitor cells
and pulmonary macrophages. This engineered lung tissue system is based on cellular repopulation and culture
of a decellularized native rat lung scaffold. This platform enables a well-controlled, native-like tissue environment
for the evaluation of cell-cell interactions, without the systemic confounders of in vivo studies. It is expected that
macrophages will significantly influence and direct epithelial remodeling by these basal-like cells, particularly in
relation to the fibrotic or anti-fibrotic activation state of the macrophages. This work expands on previous findings
that adding macrophages to engineered lung cultures containing basal-like progenitor cells significantly improves
tissue architecture and regenerative epithelial cell phenotype, compared to engineered lung cultures without
macrophages. First, pulmonary macrophages will be isolated from rats by bronchoavleolar lavage and
characterized. Protocols will be developed to chemically stimulate macrophages in vitro to a disease-like
inflammatory state, or to a reparative anti-fibrotic state. Next, macrophages of different activation states will be
introduced to air-liquid interface cultures of regenerative basal cells, to evaluate epithelial-macrophage
interactions in isolation. Finally, activated macrophages will be introduced to engineered lung cultures containing
regenerative basal cells, fibroblasts, and endothelium to recapitulate essential native cellular communities.
Engineered lung tissues will be evaluated for histologic and biomechanic changes between conditions, as well
as differential cell signaling patterns, as evaluated by single-cell RNA sequencing. It is expected that
inflammatory macrophages will contribute to fibrotic response in regenerating epithelium, whereas anti-fibrotic
macrophages will contribute to more functional alveolar regeneration by basal-like cells. The findings of this
study will elucidate the role of pulmonary macrophages in governing lung repair and regeneration in this model
system. Further, this work may suggest possible routes for the treatment of fibrotic lung diseases. The proposed
research project will be executed by Allison M. Greaney at the David H. Koch Institute for Integrative Cancer
Research at the Massachusetts Institute of Technology (MIT), under the Sponsorship of Dr. Robert Langer, and
Co-Sponsorship of Dr. Ruslan Medzhitov at Yale University. Dr. Langer a...

## Key facts

- **NIH application ID:** 10387664
- **Project number:** 1F32HL162428-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Allison Marie Greaney
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,174
- **Award type:** 1
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387664

## Citation

> US National Institutes of Health, RePORTER application 10387664, The Role of Macrophages in Pulmonary Regeneration using a Bioengineered Whole Lung Tissue Model (1F32HL162428-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10387664. Licensed CC0.

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