# Extended preservation of human livers: a nature inspired, high subzero controlled, limited freezing approach

> **NIH NIH R44** · SYLVATICA BIOTECH, INC. · 2022 · $705,323

## Abstract

ABSTRACT
1 in 5 liver waitlist patients do not receive a new liver in time, while many more patients are never listed but could
benefit from liver replacement. While “bridge-to-transplant” technologies (ventricular assist devices and dialysis)
have transformed the outlook for heart failure and kidney failure, no such treatment exists for patients with liver
failure. Current liver sharing limits (approx. 500 miles) are based on limited preservation durations (6-10 hours).
By extending preservation to just a few days we can enable nationwide (theoretically global) donor-recipient
matching, allowing many livers that go untransplanted today (e.g. subsets of extended criteria donor livers that
have been shown to offer substantial survival benefits) to be offered to the patients who most need them.
Transplant surgeons have expressed excitement about this possibility, and it is thought that this achievement
would have a profound impact on liver waitlist mortality. Among other benefits, this can also increase graft
lifespan and reduce immunological rejection, eliminate the need for costly jet and helicopter transport, transform
the practice of liver transplantation from emergency surgery to a flexibly scheduled procedure, and mitigate the
severe disparities in liver transplantation. It will also allow immune tolerance induction protocols that have now
achieved success in living donation to be adapted to the deceased donor context. To meet these needs, we
will develop a comprehensive system for banking human livers for transplantation for periods of 5-7
days with a stretch goal of 10+ days or longer. We have created an integrated two-pronged approach to
develop new stasis cocktails optimized for the critical phases of liver preservation: preconditioning and protection
(prior to storage), preservation (during storage) and revival- resuscitation-repair (after storage). In parallel, we
are creating devices for advanced perfusion, storage, and organ assessment before transplant decision. Our
approach adapts the best strategies of freeze-tolerant and hibernating species, augmenting them with recent
scientific and bioengineering advances. Importantly, we do not seek to solve all the problems of classical
cryopreservation, but rather to be the first to develop preservation in thermodynamic equilibrium at high subzero
(HSZ) temperatures (-10°C to -30°C), combined with programmed metabolic depression and enhanced stress
tolerance. Feasibility of this approach has already been demonstrated; we have banked rat livers for 5 days
at HSZ temperatures, and successfully preserved the first whole human liver lobe at -15°C. For this fast-track
proposal, the Phase 1 goal will be to further refine our protocols and validate our initial unprecedented storage
duration by banking rat livers for 5-7 days and using comprehensive post-preservation normothermic machine
perfusion with functional assessment. We will also scale to whole human liver lobes, with subsequent hepatocyte
is...

## Key facts

- **NIH application ID:** 10019132
- **Project number:** 4R44DK124053-02
- **Recipient organization:** SYLVATICA BIOTECH, INC.
- **Principal Investigator:** YOED RABIN
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $705,323
- **Award type:** 4N
- **Project period:** 2019-09-13 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019132

## Citation

> US National Institutes of Health, RePORTER application 10019132, Extended preservation of human livers: a nature inspired, high subzero controlled, limited freezing approach (4R44DK124053-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019132. Licensed CC0.

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