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

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $867,215

## Abstract

Abstract
Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity whose incidence is on the
rise associated with the increased survival of extremely preterm infants. The etiology of BPD is multifactorial
resulting from prenatal risk factors such as preeclampsia, chorioamnionitis, and perinatal insults including
oxygen exposure, infection, and mechanical ventilation. Inflammation is a key pathway underlying the
pathogenesis of BPD which can result in significant long-term multisystem morbidities, including adverse
neurological outcomes, immune dysregulation with susceptibility to infections, and pulmonary morbidities
including asthma and, in some cases, emphysematous changes that persist into adulthood. Thus, BPD is no
longer considered a lung disease of the neonatal period, but a complex condition with multiorgan involvement
and lifelong consequences. To date, effective treatments are lacking and there is a need to deliver effective
strategies for the prevention and management of BPD. Mesenchymal stem/stromal cells (MSCs) are in clinical
trials as potential cellular therapy for BPD. We and others have shown that the main therapeutic modality of
MSCs resides in their secretome represented by `small' extracellular vesicles (sEVs), an EV subset that
includes exosomes. We demonstrated that treatment with purified human MSC-derived sEvs, termed MEx,
ameliorated and even reversed core histological and functional outcomes of BPD in several experimental
models. In the neonatal hyperoxia (HYRX) murine BPD model, MEx protected other organs from injury
including the brain, retina, and the thymus whose architecture was disrupted by HYRX. We demonstrated that
MEx localize in the lung and interact with myeloid cells altering their phenotype from proinflammatory to
immunosuppressive. Importantly, adoptive transfer of in vitro MEx-educated bone marrow derived myeloid
cells, but not naïve cells, restored alveolar architecture, blunted fibrosis and vascular remodeling, and
improved exercise capacity. We hypothesize that MEx regulate the immune landscape of the developing lung
and promote a distinct macrophage phenotype that, through release of anti-inflammatory cytokines and
enhanced efferocytosis of apoptotic cells, resolves tissue inflammation and orchestrates signals to promote
lung growth disrupted by HYRX. In this proposal we plan to (1) Elucidate mechanisms by which MEx promote
the establishment of the alveolar macrophage niche and development of innate immunity that is disrupted by
neonatal HYRX; (2) Explore the functionality of lung myeloid cells instructed by MEx in resolving inflammation
and promoting lung development; and (3) Elucidate the effects of neonatal HYRX and MEx treatment on long
term immune cell function and susceptibility to airway disease.

## Key facts

- **NIH application ID:** 10792928
- **Project number:** 5R01HL146128-06
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Stella Kourembanas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $867,215
- **Award type:** 5
- **Project period:** 2019-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10792928

## Citation

> US National Institutes of Health, RePORTER application 10792928, MSC Exosome Treatment for BPD: Impact on Immunity and Lung Development (5R01HL146128-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10792928. Licensed CC0.

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