PI: Eric Lagasse
Title: Cell Therapy for Patients with End Stage Liver Disease
Description: Obesity is a complex medical condition caused by dysregulation of systemic metabolism, excessive accumulation of body fat, insulin resistance and a variety of additional health issues. Hepatocytes produce bile acids, which are recognized as key regulators of systemic metabolism, particularly systemic energy expenditure. In this pilot study, we propose experiments to transplant hepatocytes into lymph nodes of mice under fat-induced diet and compare to transplant of brown fat tissue into lymph nodes for an effective treatment of metabolic syndrome.
Statement of Work: Cell-based therapy is a promising approach to generate hepatic functions in patients suffering from a variety of liver diseases. LyGenesis Inc. is a startup company focused on developing technology that enables a patient’s own lymph nodes to be used as bioreactors for hepatocyte transplantation and regeneration of an ectopic liver.
The goal of this study is to demonstrate that transplanted hepatocytes into lymph nodes of mice under fat-induced diet could be an effective treatment of metabolic syndrome. This study will be compared to transplant of brown adipose tissue into lymph nodes.
Background and Rational: Obesity is a complex medical condition caused by dysregulation of systemic metabolism, excessive accumulation of body fat, insulin resistance and a variety of additional health issues. Hepatocytes produce bile acids, which are recognized as key regulators of systemic metabolism, particularly systemic energy expenditure. In this pilot study, we propose experiments to transplant hepatocytes into lymph nodes of mice under fat-induced diet and compare to transplant of brown fat tissue into lymph nodes for an effective treatment of metabolic syndrome.
Research Plan Overview and Approach: C57BL/6J mice will be separated in 4 groups (No high fat diet, high fat diet, high fat diet with transplantation of cells in lymph nodes, high fat diet with transplantation of cells in peritoneal fat). For the animal under high fat diet (HFD), the diet will be induced for 6 weeks. Body weight (1x/week), basal non fasting blood glucose, glucose tolerance test, serum triglyceride, low density cholesterol, and serum IGF1, IL-6 and FGF21 data will be collected before the 6 weeks HFD and at week 6 of HFD. Animal will be transplanted with cells (hepatocytes or brown adipose tissue) with continue HFD the next 8 weeks, transferred to C3M core (The Center for Metabolism and Mitochondrial Medicine) for metabolic monitoring (Sable Systems Promethion metabolic cages and GTT) and possible Insulin Sensitivity by Hyperinsulinemic Euglycemic Clamp before necropsy.
Source: LyGenesis
Term: May 1, 2022 – June 30, 2023
Amount: $257,140