# Molecular Targets of Preservation Injury Mitigated by Hypothermic Oxygenated Machine Perfusion in Liver Transplantation

> **NIH NIH R21** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $231,817

## Abstract

PROJECT SUMMARY
Liver transplantation (LT) is the only definitive cure for end stage liver disease; however, there is a growing gap
between organ demand and availability. This has led centers to rely on extended criteria donors (ECD), which
include grafts from older donors, fattier livers, or following donation after cardiac death (DCD). These grafts are
particularly vulnerable to preservation injury and carry increased risk of post-LT complications. Optimizing
organ preservation techniques would improve patient outcomes, increase utilization of ECD grafts, and
improve access to life-saving LT. Hypothermic Oxygenated Machine Perfusion (HMP-O2) provides continuous
liver flush with oxygenated preservation solution. HMP-O2 shows great promise in early clinical trials in the US
and Europe. Recipients exhibit decreased preservation injury and improved early post-LT outcomes. The exact
molecular pathways modulated by HMP-O2 remain largely undefined. Our team has pioneered machine
perfusion in LT. With a novel portable perfusion pump, the LifePort® Liver Transporter (LLT, Organ Recovery
Systems), we are the lead institution in the first US prospective, randomized controlled multi-center trial
comparing HMP-O2 vs Static Cold Storage (SCS, conventional storage on ice) in LT (NCT 03484455). Under
the continued access phase, with non-randomized enrollment of patients, we have increased utilization of ECD
grafts at our center with excellent outcomes. To characterize the molecular targets of early allograft injury, we
have paired this with an extensive longitudinal bio-specimen collection protocol. The long-term goals of the
present research are to (1) define the protective pathways activated by HMP-O2 compared to SCS and (2) to
identify target biomarkers for organ monitoring and for future therapeutic optimization of allograft function.
Initial data from our center show HMP-O2 improves post-LT morbidity. Preliminary biochemical, molecular, and
tissue injury analyses demonstrate improved tissue structural integrity, decreased inflammatory signaling, and
preserved cellular function. We hypothesize that HMP-O2 improves early allograft function and risk of
post-operative complications by decreasing inflammatory signaling, moderating cellular metabolic
dysregulation, and ultimately, promoting cellular homeostasis. Specific aims are proposed to (1)
immune cell activation, inflammatory signaling, and metabolic dysfunction mitigated by HMP-O2, as well
correlate proteogenomic markers of preservation injury between tissue and liver perfusate in HMP-O2
define
as to (2)
compared to SCS to establish thresholds of irreversible injury for ex vivo monitoring. Capitalizing on our
extensive biorepository, histologic, biochemical, genetic, and protein markers of injury will be defined in tissue
(liver and bile duct), preservation fluid effluent, and bile. We expect to see decreased markers of inflammation,
abrogated cell injury, and increased homeostasis during and following H...

## Key facts

- **NIH application ID:** 10989170
- **Project number:** 1R21AI180739-01A1
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** James V. Guarrera
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $231,817
- **Award type:** 1
- **Project period:** 2024-06-21 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10989170

## Citation

> US National Institutes of Health, RePORTER application 10989170, Molecular Targets of Preservation Injury Mitigated by Hypothermic Oxygenated Machine Perfusion in Liver Transplantation (1R21AI180739-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10989170. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*