# Incorporating hepatic cell function into lung ex vivo lung perfusion for transplant preservatio

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2024 · $167,908

## Abstract

ABSTRACT RESUBMISSION 1R21 HL164436-01 IN RESPONSE TO NHLBI “NOT-HL-21-024
BOLD AND NEW BIOENGINEERING RESEARCH”
In contrast with other organs, preservation times of lung grafts for transplantation are limited to
no more than 8 hours with standard cold preservation. Declining quality with extending
preservation times increases the risk of primary graft dysfunction, a risk factor for developing
chronic rejection, which could account for the low 5-year survival rate (50%) following lung
transplantation (LTx). Ex Vivo Lung Perfusion (EVLP) is expected to improve lung preservation
and transplant outcomes by providing normothermic circulation and ventilation. A problem is that
current EVLP is self-limited by normothermia-activated lung metabolism. The accumulation of
toxic metabolites leads to a proinflammatory state, activating Receptor of Advanced Glycation
End-Products (RAGE) and nuclear factor (NF)-B mechanisms, which in turn upregulate
proinflammatory cytokine signaling. Experimentally, cross-circulation of a whole swine with EVLP
by others demonstrated improved lung resuscitation, but the exact contributors to this
improvement remain unclear. Own in vitro preliminary data suggest a role for hepatic function in
enhancing endothelial preservation. In previous work, we have maintained normal hepatic
detoxification, synthesis, and regulation in in vitro circuits using liver cell bioreactors (BRx). We
hypothesize first that the liver function in the swine cross-circulation model played a major role
in enhancing EVLP and tissue viability. We also hypothesize that a hepatocyte BRx can partly
substitute for whole-swine liver function on EVLP and maintain the observed improvements lung
preservation and LTx outcomes. Our Specific Aim is to provide proof-of-principle for the ability
of hepatocyte BRx to enhance lung graft preservation. We will incorporate a hepatic BRx in our
established EVLP circuits and demonstrate its effect on short-term LTx in experimental rat
models. We will repeat these experiments using a cadaveric human EVLP model. We will conduct
comprehensive phenotypic, transcriptional, and functional endpoint assessments on lung tissue
and hepatic cells in BRx, such as RAGE and NF-B. If successful, our technology will provide the
means to change the current state of EVLP for lung preservation and allow lungs to be maintained
longer outside the donor body with less cellular injury. Ultimately, our work will address current
limitations in LTx, including increasing viable donor organ transportation time and distance,
helping reduce LTx waiting lists, and improving post-transplant patient survival.

## Key facts

- **NIH application ID:** 11099018
- **Project number:** 7R21HL164436-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Pablo G Sanchez
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $167,908
- **Award type:** 7
- **Project period:** 2024-05-31 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11099018

## Citation

> US National Institutes of Health, RePORTER application 11099018, Incorporating hepatic cell function into lung ex vivo lung perfusion for transplant preservatio (7R21HL164436-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11099018. Licensed CC0.

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