Extended 78&#37; Hepatectomy in a Mouse Surgical Model

Phillip Brennan; Nyah Patel; Tarek Aridi; Michelle Zhan; Cleide Angolano; Christiane Ferran

doi:10.3791/66528

Extended 78% Hepatectomy in a Mouse Surgical Model

JoVE Journal
Biology

A subscription to JoVE is required to view this content. Sign in or start your free trial.

JoVE Journal Biology

Extended 78% Hepatectomy in a Mouse Surgical Model

Full Text

3,791 Views

05:25 min

May 24, 2024

DOI: 10.3791/66528-v

Phillip Brennan¹, Nyah Patel¹, Tarek Aridi¹, Michelle Zhan¹, Cleide Angolano¹, Christiane Ferran^1,2

¹Division of Vascular and Endovascular Surgery and the Center for Vascular Biology Research, Department of Surgery,Beth Israel Deaconess Medical Center and Harvard Medical School, ²The Transplant Institute and the Division of Nephrology, Department of Medicine,Beth Israel Deaconess Medical Center and Harvard Medical School

Overview

This study investigates a mouse model of an extended 78% hepatectomy, which better mimics small-for-size syndrome after liver transplantation. The findings indicate a postoperative survival rate of approximately 50% in healthy mice, contrasting sharply with the near 100% survival associated with traditional two-thirds partial hepatectomy.

Key Study Components

Research Area

Liver regeneration and repair
Liver transplantation
Therapeutic strategies for enhancing outcomes

Background

Extended hepatectomies have rarely been explored in literature.
Marginal liver grafts and their risks in transplantation settings are critical challenges.
A focus on gene therapy for hepatocyte protection and regeneration is at the forefront of this research.

Methods Used

Mouse model of extended hepatectomy
Liver-targeted gene therapy
Genomic and proteomic platforms for studying liver biology

Main Results

Successful implementation of a surgical procedure resulting in 50% postoperative survival.
A20 gene therapy demonstrated hepatoprotective functions, improving survival outcomes.
Model serves as a basis to study small-for-size syndrome and therapeutic interventions.

Conclusions

Investigating extended hepatectomies can lead to improved understanding and therapies for liver conditions.
This model can significantly contribute to optimizing liver transplantation strategies.

Frequently Asked Questions

What is the significance of the 78% hepatectomy model?

This model simulates small-for-size syndrome more accurately, allowing research into liver transplantation challenges.

How does the A20 gene therapy work?

A20 provides hepatoprotection through anti-inflammatory and anti-apoptotic mechanisms, enhancing liver regeneration.

What are the postoperative outcomes of the procedure?

The procedure results in approximately 50% postoperative survival compared to nearly 100% in traditional methods.

What are potential applications of this research?

This research could lead to improved therapeutic strategies for liver transplantation and cancer surgeries.

What technologies are utilized in this study?

The study employs genomic, proteomic, and metabolomic platforms to analyze liver regeneration.

Why is liver regeneration important?

Understanding liver regeneration is crucial for improving outcomes in liver diseases and surgeries.

What are the implications for clinical translation?

Pretranslational studies in large animals may pave the way for clinical trials of A20 gene therapies.

The mouse model of partial 2/3 (66%) hepatectomy is well described in the literature, but more extended hepatectomies mimicking small-for-size syndrome after liver transplantation have seldom been used. We describe an extended 78% hepatectomy procedure in a mouse model that results in approximately 50% postoperative lethality in healthy mice.

The scope of our research is to evaluate therapeutic strategies to enhance liver regeneration and repair that could aid in improving patients'outcomes in the setting of liver transplantation using marginal liver grafts as well as extended liver resection for cancer that are at higher risk for primary non-function and acute hepatic failure. Our team utilizes genomic, proteomic, and metabolomic platforms to study liver regeneration and identify novel therapeutic targets to improve outcomes. The focus of our laboratories is to develop state-of-the-art gene therapy platforms to deliver the hepatoprotective and liver regenerative gene A20.

We uncovered a potent hepatoprotective function for A20, also called TNFAIP3, through its combined anti-inflammatory, anti-apoptotic, and proproliferative functions in hepatocytes. Liver-targeted A20 gene therapies protected from lethality in mouse models of toxic hepatitis, extended 78%and lethal radical hepatectomies 90%and also prolonged liver ischemia. Recent promising pretranslational studies in large animal prelude clinical translation of this therapy.

View the full transcript and gain access to thousands of scientific videos