# High subzero preservation of liver for transplantation

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $384,750

## Abstract

PROJECT SUMMARY
With more than five times the number of patients on the wait list than will receive a donor organ in the United
States, the field of transplantation is facing a serious donor shortage crisis. Overcoming the organ shortage will
require integrated strategies, including a particular focus on overcoming ineffective bio-preservation and
stabilization protocols. Longer storage durations will provide the infrastructure required to enable global
matching programs, eliminate the need to scramble and conduct unplanned surgeries, and reduce unnecessary
waste of quality organs.
We believe the method for preserving mammalian organs should employ hibernating and freeze-tolerant
strategies in nature that are then further augmented using bioengineering principles. Consequently, we seek to
develop a protocol for human organ preservation which will achieve high subzero storage
temperatures (ranging from -10 to -20 °C) in the presence of extracellular ice, and storage durations of
weeks to months, using inspiration from in nature. Our approach is unique in organ/tissue preservation
literature since we aim to actively initiate ice propagation in the vasculature and extracellular spaces, rather
than extreme means of inhibiting ice crystallization as is the current standard. The presence of non-injurious
ice will be essential in achieving longer storage durations, while also playing an important role in the scale-up
to human livers. While this program targets the banking of human liver, our discoveries and solutions will be
translatable to other tissues and organ systems.
In Specific Aim 1, we will adapt endothelial cell-coated microvascular networks already developed by our
group3 in order to model and develop strategies to overcome challenges associated with ice propagation.
Since endothelial cells in the vasculature will be the most vulnerable to ice propagation, SA#1 will be an
essential proof of concept of our novel strategy and we already have promising data. In Specific Aim 2, we will
engineer an ice nucleating agent which will promote non-injurious propagation of ice in extracellular spaces.
Ice nucleating agents are essential for restricting ice formation to extracellular spaces and have been identified
as critical strategies for freezing survival. In Specific Aim 3, we will reprogram cells to descend into a state of
`suspended animation' with enhanced stress tolerance, as inspired by nature. We will achieve this using both
passive temperature effects as well as using pharmacological agents. We will perform in-depth
characterization of the molecular impact of our cellular reprogramming efforts. In each specific aim, we scale
up rapidly to rat whole liver while also validating in human livers in order to maximize impact.

## Key facts

- **NIH application ID:** 9898358
- **Project number:** 5R01DK114506-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mehmet Toner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,750
- **Award type:** 5
- **Project period:** 2017-07-17 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898358

## Citation

> US National Institutes of Health, RePORTER application 9898358, High subzero preservation of liver for transplantation (5R01DK114506-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898358. Licensed CC0.

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