Generation of Organotypic Liver Cultures for the Identification of Biomarkers for the Prevention and Treatment of Liver Fibrosis

Hepatic Fibrosis Clinical Trial

Official title:

Generation of Organotypic Liver Cultures for the Identification of Biomarkers for the Prevention and Treatment of Liver Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06252272
• Other study ID #: RS1822/23
• Status: Recruiting
• Phase: N/A
• Start date: January 17, 2023
• Est. completion date: January 17, 2025

Study information

• Verified date: February 2024
• Source: Regina Elena Cancer Institute
• Contact: Silvia Soddu, Doctor
• Phone: 06 5266 2492
• Email: silvia.soddu[@]ifo.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Low-level, interventional, biological and non-pharmacological study prospective intervention for the preparation of organotypic human liver slice cultures Liver Slice Culture (hLSC) applying the protocol described by Jiang and collaborators.

Description:

Human liver slice culture hLSCs will be used from non-tumor liver tissue collected by biopsy from patients undergoing abdominal surgery, who have signed informed consent and agree to perform a liver biopsy for the specific research protocol.

The study is "low level interventional" when a small portion (approximately 10 mm in diameter) of liver tissue macroscopically free from parenchymal alterations obtained in the open at the site of surgery for primary or secondary liver tumors will be taken (hepatic metastases from colorectal, pancreatic or breast cancer). The goal is to create organotypic liver cultures (hLSC) derived from liver biopsies taken from patients undergoing abdominal surgery.

for primary or secondary liver tumors for the molecular characterization of liver fibrosis.

Use hLSC to study the liver microenvironment and molecular determinants involved in fibrosis through single cell sequencing; compare the sequencing data obtained with hLSC with that obtained via characterization of a GEMM whose generation is foreseen in the same project financed by the MoS.

To generate this GEMM, the pro-fibrotic Hipk2 gene was specifically deleted in the tissue liver (HIPK2-liver knock-out, HIPK2-LKO) and liver fibrosis will be induced through a high-fat, low-choline diet.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: January 17, 2025
• Est. primary completion date: January 17, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• age over 18 years old;

• patients for whom it is indicated to undergo abdominal surgery for tumors primary or secondary liver diseases;

• patients who express informed consent to the study.

Exclusion Criteria:

• medical contraindication to performing a liver biopsy;

• liver cirrhosis;

• macroscopic signs of chronic liver disease;

• moderate or severe steatosis;

• cholestasis;

• hepatic necrosis.

Related Conditions & MeSH terms

• Fibrosis
• Hepatic Fibrosis
• Liver Cirrhosis

Intervention

Diagnostic Test:
• Biopsy from patients undergoing surgery abdominal.
A small portion (about 10 mm in diameter) of liver tissue was collected macroscopically free from alterations of the parenchyma obtained in the open at the site surgery for primary or secondary liver tumors, for the preparation of cultures of organotypic liver slices.

Locations

Country	Name	City	State
Italy	"Regina Elena" National Cancer Institute	Rome

Sponsors (2)

Lead Sponsor	Collaborator
Regina Elena Cancer Institute	Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Molecular characterization of liver fibrosis	Creation of organotypic cultures of liverderived from liver biopsies taken from patients undergoing abdominal surgery for primary or secondary liver tumors for the molecular characterization of liver fibrosis.Patients will undergo abdominal surgery (as per clinical practice), during which a biopsy will be performed in an area of the liver macroscopically free from parenchymal alterations, approximately 20/25 slices will be obtained from each sample. The hLSCs will come used to study the hepatic microenvironment in the presence or absence of pro-fibrinogenetic stimuli e of anti-fibrotics by time-lapse analysis and confocal immunofluorescence microscopy multiple and through single cell sequencing.	24 months
Secondary	Study of the hepatic microenvironment	Use hLSCs to study the liver microenvironment and the molecular determinants involved in it fibrosis through single cell sequencing (single-cell RNA sequencing);	24 months
Secondary	Compare the sequencing data	Compare the sequencing data obtained with hLSCs with those obtained through the characterization of a GEMM. A biopsy will be performed after abdominal surgery (as per clinical practice), in an area of the liver macroscopically free from parenchymal alterations.; hLSCs will be analyzed over the following week for viability and fibrosis induction using fibrosis-specific stains for time-lapse dynamic imaging (IncuCyte), i.e. picrosirius red, Masson's trichrome, and quantitative RT-PCR and multiplex immunofluorescence	24 months