# High subzero preservation of liver for transplantation

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $551,075

## Abstract

ABSTRACT
 With more than five times the number of patients on the wait list than will receive a donor organ in the USA, the
field of transplantation is facing a serious donor shortage crisis. Despite decades of research, a major critical bottleneck is
the current preservation times for whole organs are limited to few hours of storage. Longer preservation times are required
to enable global matching programs, eliminate unnecessary waste of organs, and reduce costs associated with unplanned
surgeries, and are enabling for mixed-chimerism based tolerance induction protocols which require the donor organ to be
kept viable for days so that recipient preconditioning can be done safely. Consequently, the focus of this application is to
address a major unmet need in transplantation by prolonging the length of time organs can be kept in “suspended
animation” ex vivo. Our approach is inspired by the hibernating and freeze-tolerant animals in nature. We aim to embrace
and control the ice formation to achieve high subzero storage temperatures in the presence of extracellular ice, and storage
durations of weeks to ultimately months. It is our hypothesis that the presence of ice in a non-injurious frozen state
enables storage at lower temperatures (down to -30°C) and consequently a deeper metabolic stasis for weeks, while also
enabling scale-up to human organs. In the previous funding period, we developed a new method to use ice nucleating
bacteria to tightly control ice formation temperature and developed a partial freezing protocol down to -15°C that can
store rat livers up to 5 days with ex vivo function, and also established a proof-of-concept in human livers. In this
competing renewal application, we propose to build on our success and reach preservation temperatures down to -30°C,
thus achieving suspended animation for weeks. We propose (i) to control ice formation in liver, which our prior studies
demonstrated to be a key barrier; (ii) to develop targeted approaches to improve preservation of endothelium, which are at
the interface of tissue and ice and are the first point of injury, and (iii) to develop a choreographed metabolic protocol to
maximize ATP recovery and improve viability of the grafts for transplant.

## Key facts

- **NIH application ID:** 10220401
- **Project number:** 2R01DK114506-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mehmet Toner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $551,075
- **Award type:** 2
- **Project period:** 2017-07-17 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220401

## Citation

> US National Institutes of Health, RePORTER application 10220401, High subzero preservation of liver for transplantation (2R01DK114506-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10220401. Licensed CC0.

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