A New Molecular Mechanism to Bioengineering a Liver

NIH RePORTER · NIH · R01 · $414,439 · view on reporter.nih.gov ↗

Abstract

Hepatocyte transplantation has many potential applications. Extensive animal experiments have shown that hepatocytes transplanted in the liver or at ectopic sites survive, function, and actively participate in the regenerative process. However our understanding of hepatocyte engraftment and their remarkable proliferative and regenerative potential is limited, even if primary hepatocyte transplantation is at the doorstep of applications in the treatment of inherited and acquired human diseases. We previously made a serendipitous observation that normal hepatocytes transplanted in the peritoneal cavity of an animal with lethal liver disease migrate into the lymphatic system and engineer ectopic liver-like organoids that rescue an animal model from a fatal metabolic disorder. How hepatocytes enter the lymphatics and what molecular mechanism is responsible for the generation of ectopic mass is not known. We hypothesized that hepatocytes must borrow some of the molecular mechanism lymphocytes use to migrate into the lymphatics. Our interest will be to study ectopic cell transplantation and our central objective of our application is to translate a highly interesting observation, the generation of ectopic liver, to a potential clinical application for patients with liver diseases.

Key facts

NIH application ID
9962971
Project number
5R01DK114282-03
Recipient
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Principal Investigator
ERIC LAGASSE
Activity code
R01
Funding institute
NIH
Fiscal year
2020
Award amount
$414,439
Award type
5
Project period
2018-04-01 → 2023-03-31