# Preservation and Rescue of The Lung Donor Allograft for Transplantation

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $672,533

## Abstract

PROJECT SUMMARY
Lung transplant surgery is the only definitive therapy for end-stage lung disease. While the waiting list of
patients eligible for transplant grows, the number of suitable donor organs falls far short of the demand. A
significant adverse event that occurs after lung transplantation is primary graft dysfunction (PGD); ischemia-
reperfusion (IR) induced cellular injury and tissue degradation play a significant role in PGD. As a community,
we throw away ~80% of the potential lung donors out of fear of an adverse PGD outcome. An agent to reduce
ischemic damage to organs and repair them prior to transplantation will represent a technology that can
preserve lung integrity, resuscitate marginal donor organs, and improve the overall positive impact of
transplantation. Previously we identified MG53 that functions as an essential component of cell membrane
repair machinery. Genetic ablation of MG53 (mg53-/- mice) leads to increased susceptibility of the lung to
stress induced injuries. Transgenic mice with sustained elevation of MG53 in the bloodstream (tPA-MG53 mice)
live a healthy lifespan with enhanced regenerative capacity following injury to multiple organs. The
recombinant human MG53 protein (rhMG53) has great potential in prevention and protection of injuries to the
lung, heart and kidney in rodent and large animal models. Using ex-vivo lung perfusion (EVLP) as a platform
for delivering therapeutic proteins, we show that rhMG53 improves lung donor integrity by mitigating injuries to
both alveolar and endothelia cells. This project builds on the scientific premise that targeting the elemental
process of cell membrane repair represents a potential novel means to preserve the quality of the lung donor,
which shall improve the outcome of lung transplantation (e.g. reduction of PGD). We will conduct lung
transplants between donor and recipient mg53-/- and tPA-MG53 mice to define the physiologic role of MG53 in
lung protection associated with IR injury (Aim 1). We will use cellular, molecular and live cell imaging tools to
derive a mechanistic base for how circulating MG53 preserves the endothelial cell integrity, improves cell
survival and reduces inflammation during IR; these studies will also establish a set of bio-markers modulated
by rhMG53 that can quantifiably predict lung injury prior to transplantation (Aim 2). In Aim 3, we will establish
the quality controls for production and formulation of rhMG53 for pulmonary applications, and use EVLP as a
delivery vehicle to test the efficacy of rhMG53 in rescuing the injured lung allograft derived from pigs and
humans. Finally, we will test in a porcine model of lung transplantation whether addition of rhMG53 during the
preservation process or after transplantation can have beneficial effects on prevention of PGD.

## Key facts

- **NIH application ID:** 10441430
- **Project number:** 5R01HL143000-05
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Bryan A Whitson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $672,533
- **Award type:** 5
- **Project period:** 2018-07-15 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441430

## Citation

> US National Institutes of Health, RePORTER application 10441430, Preservation and Rescue of The Lung Donor Allograft for Transplantation (5R01HL143000-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10441430. Licensed CC0.

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