TODAY Online

Fall 2002

Bioartificial Liver Being Studied at Center
By Anne Taguchi
University of Southern California

There are no effective medical treatments for cirrhosis except liver transplantation. With limited donor livers available, many cirrhosis patients die while waiting for liver donors or because they cannot afford the only life-saving surgery. In collaboration with a Japanese biotech company, Able Corp., the Center's Cirrhosis Research Program has acquired a radial flow bioartifical liver system to test whether it optimizes reconstitution of functional liver tissues.


The USC Cirrhosis Research Program has begun growing hepatocytes and non-parenchymal liver cells isolated from rats to experimentally test the central concepts in the radial-flow bioreactor system. The program currently has two 30ml bioreactor systems and four 5ml systems being used for on-going studies.


Liver cells are grown onto hydroxyapatite beads. Unique from other systems, the beads allow the cells to grow three dimensionally rather than on a two-dimensional flat surface.

PHOTOS COURTESY OF ABLE CORP.

The director of the program, Dr. Hide Tsukamoto, has a long-standing interest in studying the pivotal role of hepatic stellate cells (HSC) in both the maintenance of normal liver cell functions and the genesis of cirrhosis. His team, including Drs. Shigang Xiong and Jiaohong Wang, is incorporating HSC and other non-parenchymal liver cells into the system to promote growth and differentiation of hepatocytes, the parenchymal cells. Says Tsukamoto, "There has been a surging interest in the development and application of bioartificial liver for the treatment of patients with cirrhosis or acute fulminant hepatitis as a conjunctive measure to support these patients while waiting for liver transplantation. Even though several clinical trials have been under way, the outcomes of these studies are in general limited due mainly to fundamental problems."

These problems include use of cancerous liver cells which are not fully functional liver cells or cells derived from other species such as pig. Even when hepatocytes freshly derived from human livers are used, they quickly become de-differentiated because the device cannot provide the best environment for the cells to maintain their liver-specific functions.

L-R: Dr. Michael Lai of USC; Mr. Yohichi Ishikawa, President of Able Corp.; Dr. Hideki Aizaki Postdoctoral Fellow in Dr. Lai's laboratory; Mr. Tomokatsu Hongo of Able Corp.; and Dr. Hide Tsukamoto, Director of the Center.

"To this end," says Tsukamoto, "there are two main problems. Firstly, the conventional systems do not incorporate non-parenchymal liver cells such as HSC, which produce unique micro-environment for optimal functions of hepatocytes. Secondly, most systems are based on hollow fibers as in a hemodialysis unit, which anatomically do not reproduce physiological blood flow and cell arrangement in the liver."

"It really makes sense to recapitulate the radial-flow arrangement and communication between different cell types seen in the liver in a bioartifical liver system to maximize its physiological functions. The bioreactor system recently acquired is currently the best prototype to meet these specific requirements."

In conjuction with the bioartifical liver project, the Program is developing novel and innovative modalities for the treatment of cirrhosis with gene therapy.