# Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosis

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $399,750

## Abstract

PROJECT SUMMARY
The ability of mesenchymal stromal cells (MSCs) to adapt to their tissue niche and remodel extracellular matrix
(ECM) could be therapeutically beneficial in treating fibrotic diseases. However, leveraging this property has
been challenging because MSCs are rapidly cleared from tissue once delivered. Thus, specific pathways to
induce MSCs to remodel the ECM and the utility of these remain unclear. We described herein a highly
efficient approach to encapsulate single cells in engineered microgels with predefined biochemical and
biophysical cues. We have fine-tuned this approach to show that clearance of MSCs is significantly delayed
when they are delivered in thin microgels intratracheally to lungs. Importantly, our preliminary data show that
this treatment decreases collagen accumulation in a murine lung fibrosis model. We show in these supporting
studies amplified ability of MSCs to degrade collagen-I when the cells are encapsulated in engineered
hydrogels with tunable stiffness. In this my first RO1 proposal, I will build upon these results to test the
hypothesis that programming of MSCs using specifically engineered microgels activates the potential of MSCs
to promote resolution of fibrosis and thus restore lung function. In Aim 1, we will determine the role of
microencapsulation in controlling retention of MSCs in lungs and facilitating resolution of lung fibrosis. In Aim 2,
we will determine the potentially important role of the inflammatory cytokine tumor necrosis factor-α (TNFα) in
modifying the phenotype of microencapsulated MSCs to produce high amounts collagenases with enhanced
potential to resolve lung fibrosis. We predict that selectively activating TNF receptor 2 in MSCs encapsulated in
soft microgels can resolve lung fibrosis. The project is highly multidisciplinary in that it will employ a
combination of expertise in biomaterials, lung fibrosis, biophysical, genetic, and mouse in vivo approaches to
address the specific aims. The results will help to define how MSCs can facilitate resolution of fibrosis through
prolonging their in vivo residence time in lungs, and modifying their phenotype through encapsulation in
engineered and tunable microgels to optimize their production of collagenases. We thus hope to develop novel
MSC based approaches to remodel aberrant extracellular matrix and to treat lung fibrosis.
!

## Key facts

- **NIH application ID:** 9894836
- **Project number:** 5R01HL141255-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jae-Won Shin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $399,750
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894836

## Citation

> US National Institutes of Health, RePORTER application 9894836, Encapsulation of mesenchymal stromal cells in engineered microgels for resolution of lung fibrosis (5R01HL141255-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894836. Licensed CC0.

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