# Tissue Engineering Resource Center

> **NIH NIH P41** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $467,004

## Abstract

Acute respiratory syndrome distress syndrome (ARDS) is the most severe complication of coronavirus disease 2019
(COVID-19), caused by a betacoronavirus, SARS-CoV-2. Patients with ARDS secondary to COVID-19 often require
mechanical ventilation support, and unfortunately present a mortality of more than 20% (23,24,25). Mesenchymal stromal
cell (MSC) therapies have been under consideration for treating a wide range of inflammatory conditions due to their
immunomodulatory capacity, hypoimmunogenic status, and excellent safety profile. MSC therapy is now gaining
additional attention as a potential approach to suppressing the cytokine storm induced by COVID-19 (28), as the
morbidity of COVID-19 is associated with strong inflammatory response to SARS-CoV-2 infection, which induces
swelling of the lung, infiltration of inflammatory cells, and non-cardiogenic pulmonary edema that limits gas exchange in
the distal lung. At this time, over 20 clinical trials for treating COVID-19 with MSCs have been registered with
ClinicalTrials.gov. Intravenous administration of allogeneic MSCs in a small group of COVID-19 patients in China [11]
indicated that the systemic inflammation was markedly suppressed and followed by improved clinical symptoms. The
study proposed here as a 1-year supplement to our P41 EB27062 grant is designed to leverage, extend and combine our
methodologies for derivation of immunomodulatory MSCs [19,20] and whole-lung bioengineering [3,4,6-9,14,15]
towards establishing an effective modality for treating and preventing the progression of COVID-19 ARDS. Specifically,
we aim to address three critical questions that would lead to the effective use of MSCs with a simplified regulatory path,
to prevent and treat the COVID-19 ARDS. Question 1: Can the ability of MSCs to suppress the cytokine storm preceding
ARDS be enhanced by cell priming with hypoxia and interferon-γ? Question 2: Given that the MSCs act largely by the
factors they produce, would exosomes from primed MSCs simililarly have enhanced immunomodulatory effects?
Question 3: Can MSC-exosomes be effectively used during the early stages of ARDS and delivered by nebulization
directly into the lung? To this end, we will pursue three specific aims in an integrated fashion, by extending and
leveraging the technologies developed in the parent grant, and using our highly translational swine model of ARDS to
establish a novel ARDS treatment.

## Key facts

- **NIH application ID:** 10213718
- **Project number:** 3P41EB027062-02S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Gordana Vunjak-Novakovic
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $467,004
- **Award type:** 3
- **Project period:** 2020-07-27 → 2021-07-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213718

## Citation

> US National Institutes of Health, RePORTER application 10213718, Tissue Engineering Resource Center (3P41EB027062-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10213718. Licensed CC0.

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