Ex vivo Human Liver Hyperperfusion Model
Research type
Research Study
Full title
Ex vivo Human Liver Hyperperfusion Model to Identify Targeted Therapies for Prevention of Small for Size Syndrome
IRAS ID
321850
Contact name
David Beech
Contact email
Sponsor organisation
University of Leeds
Clinicaltrials.gov Identifier
Version 1.1, Date: 20/07/2023, Study Technical Protocol
Duration of Study in the UK
2 years, 11 months, 31 days
Research summary
Liver is the only solid organ that regenerates following surgical removal of part or transplantation of a portion of donor liver. The underlying pathophysiology is poorly understood. Most of the research is based on small animal studies, findings of which do not translate accurately to human liver regeneration.
Regeneration is triggered by increased blood flow through small portion of the remnant/transplanted liver. Excessively high blood pressure in relatively smaller liver portion can cause mechanical damage to cells lining blood vessels. Regeneration or tissue damage depends on the ability of liver to cope with blood pressure changes. Tissue damage may result in Small for Size Syndrome (SFSS), which can cause liver failure. It is well known that patients with SFSS have higher mortality risk (upto 16%) compared to other patients. We recently discovered a protein called PIEZO1 expressed in cells lining blood vessels. It responds to increased blood flow, stimulates formation of new blood vessels and has a potential role in regeneration. PIEZO1 can be activated by chemical drugs, offering us the potential to explore PIEZO1 modulation to prevent liver failure. Machine perfusion circuits are used clinically to preserve donor livers before transplantation. They can regulate blood flow rate/pressure. They can be used innovatively in laboratory to study the effects of blood perfusion pressure on liver cell injury/regeneration.
Our aim is to develop a human liver hyperperfusion model. We will reproduce anatomical changes to livers on machine using surgical/radiological techniques, as would happen after a major cancer resection/partial liver transplant. We hypothesize that the same amount of blood flowing through a smaller segment will simulate the excess perfusion that happens after surgery. This model will further be used to explore role and activity of PIEZO1 in liver regeneration. Our research will be the first step towards graft reengineering to obtain survivable livers.
REC name
North West - Greater Manchester West Research Ethics Committee
REC reference
23/NW/0361
Date of REC Opinion
19 Dec 2023
REC opinion
Further Information Favourable Opinion