HepaHope Product Publications
American Society for Artificial Internal Organs (ASAIO)
June 8-10, 2006
CHICAGO, USA
Characterization of a Novel Porcine Liver Slice-Filled Bio-artificial Liver (BAL) For Treatment of Liver Failure Patients
Holger P. Behrsing1, Jennifer Tam1, Brad Gray1, Andy Do1, Delai Zhao1, Jaeho Jung1, Rik Bundey2, Robert G. Gish3, Brendan M. McGuire4, Dong-Jin Suh5, Sung-Soo Park1
1Research and Clinical Development, HepaHope Inc., Irvine, CA, 2Department of Pharmacology, UCSD, La Jolla, CA, 3Medicine, California Pacific Medical Center, San Francisco, CA, 4Medicine, University of Alabama, Birmingham, AL, 5College of Medicine, University of Ulsan, Seoul, Korea
A large number of patients die annually from liver failure worldwide. A new high capacity HepaHope BAL is designed to treat such liver failure patients as a potential life-saving alternative. The BAL contains porcine liver slices with multiple, native cell types in well-preserved structures that allows efficient biochemical function and removal of toxins from blood plasma. Several in vitro and in vivo studies on animals to characterize the BAL have been conducted. Both types of studies involved a 3-hour incubation to revive cold-stored tissue prior to a 6-hour treatment when the efficacy, safety, and functionality were assessed. Results from in vitro experiments indicated that 24-hr cold-stored BALs are functional and that minimal porcine protein effluent over ~90 kDa is detected in medium (SDS-PAGE). Clearance of 1000 µg/dL ammonia was similar using human (2.7 ml/min/kg) to porcine (3.0 ml/min/kg) plasma. Minimal staining of anti-GAL was seen histologically. The percent clearance of a panel of commonly administered drugs was significant but varied between drugs during a simulated treatment. In vivo experiments using an acute liver failure canine model demonstrated a 2.5-fold increase of survival time over control dogs that had BAL devoid of porcine liver slices. Porcine endogenous retrovirus susceptibility test is currently underway.
