Development of novel ex vivo models of liver disease.
Research type
Research Study
Full title
Development of novel ex vivo models of liver disease for the identification of new therapeutic targets, biomarkers and bioengineering approaches.
IRAS ID
222302
Contact name
Nigel David Heaton
Contact email
Sponsor organisation
King’s College Hospital NHS Foundation Trust
Duration of Study in the UK
4 years, 11 months, 30 days
Research summary
There is an urgent need for reliable and reproducible experimental models in order to study the diseases affecting the liver, such as fatty liver disease, fibrosis development, viral hepatitis and alcohol-induced liver disease.
The experimental models currently utilized in liver research are mainly based on cell cultures or animal models, such as rodents which do not mimic or recapitulate the complex pathogenesis of liver injury and disease progression that occurs in humans, in particular the processes leading to fibrosis and cirrhosis in humans cannot be replicated.
The lack of this understanding hinders the development of therapies and biomarkers both prognostic and diagnostic. Moreover, the pre-clinical testing of new molecules in these models have shown only limited translation into new drugs, showing inadequate efficacy when tested in humans.
This current study will develop novel systems to study the liver based on the culture of living human liver tissue, which will maintain the main characteristics of the organ in vivo.
By building on previously established expertise we will utilise excess liver tissue, which would be otherwise discarded after surgical operation such as explants or tissue from partial hepatectomy (diseased and healthy portions), to obtain precision cut liver slices (PCLS) and to extract the extracellular matrix (ECM) in order to develop these innovative models.
The systems will also be enhanced to incorporate the use of immune cells (from blood of the same donor) in order to recapitulate inflammation, an important component of liver diseases.
We plan to use these models to understand the pathogenesis of liver injury from different aetiologies and will investigate the immunological, molecular, regenerative and intracellular pathways associated with toxic and viral-induced injury including fibrosis, cirrhosis, cancer and metastases in the liver in order to identify biomarkers of disease and novel therapeutic targets.REC name
North East - York Research Ethics Committee
REC reference
17/NE/0340
Date of REC Opinion
18 Oct 2017
REC opinion
Favourable Opinion