# MSC Exosome Treatment for BPD: Impact on Immunity and Lung Development

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2021 · $772,586

## Abstract

ABSTRACT
Bronchopulmonary dysplasia (BPD) is a multifactorial chronic lung disease of preterm infants. With no single
effective therapy for either the prevention or treatment of BPD, the need for new tools to treat and reduce risk
of further complications associated with extreme preterm birth is urgent. Indeed, mesenchymal stromal/stem
cell (MSC) therapy had shown promise in preclinical models of BPD, however more recent studies have
established that the main therapeutic vectors of MSCs is comprised in their secretome and represented by
exosomes. Exosomes are submicron, lipid bilayer-enclosed extracellular vesicles (EVs) expressed by most
cells. Their varied origin, biogenesis and molecular composition enroll them in diverse and potent physiological
roles, the most intriguing of which is an effective method of cell-to-cell communication. The MSC exosome
composition has been reported to include small noncoding RNAs, free fatty acids, surface receptors and
proteins, serving as vectors of MSC therapeutic effects. Consequently, in addition to their diverse roles in
health and disease, exosomes represent novel reagents for therapeutic applications. We isolated exosomes
from human MSC conditioned media, termed MEx, and showed that they inhibit BPD in the neonatal hyperoxia
mouse model. Specifically, one dose of Mex inhibits lung inflammation, alveolar injury, pulmonary
hypertension, fibrosis, and normalizes long-term lung function. We have demonstrated that MEx are taken up
by macrophages (Mφs) and, as result, shift the Mφ phenotype to inflammation resolving, antifibrotic, and anti-
remodeling. We hypothesize that Mφs are key vectors of MEx therapeutic action, orchestrating cell-to-cell
communication signals to promote normal alveogenesis and to restore lung homeostasis. We will test this
hypothesis in the following specific aims: SA#1: To isolate and comprehensively characterize MEx
subpopulations and investigate mechanisms of their action and biological potency in vitro and in vivo; SA#2: To
test the role of monocytes/Mφs as mediators of MEx signals to lung cells; SA#3: To investigate the biologic
function of monocytes/Mφs, modified by MEx, on hyperoxia-induced BPD in vivo.

## Key facts

- **NIH application ID:** 10117047
- **Project number:** 5R01HL146128-03
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Stella Kourembanas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $772,586
- **Award type:** 5
- **Project period:** 2019-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117047

## Citation

> US National Institutes of Health, RePORTER application 10117047, MSC Exosome Treatment for BPD: Impact on Immunity and Lung Development (5R01HL146128-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10117047. Licensed CC0.

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