Jaime M Glorioso1, Shennen A Mao1, Brian Rodysill1, Taufic Mounajjed2, Walter K Kremers3, Faysal Elgilani4, Raymond D Hickey5, Hakon Haugaa6, Christopher F Rose7, Bruce Amiot8, Scott L Nyberg9. 1. Department of Surgery, Mayo Clinic, Rochester, MN, USA. 2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA. 4. William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA. 5. William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA; Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA. 6. Department of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway. 7. Hepato-Neuro Laboratory, CRCHUM, Universite de Montreal, Quebec, Canada. 8. Brami Biomedical, Inc., Minneapolis, MN, USA. 9. Department of Surgery, Mayo Clinic, Rochester, MN, USA; William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, USA. Electronic address: nyberg.scott@mayo.edu.
Abstract
BACKGROUND & AIMS: The neuroprotective effect of the spheroid reservoir bioartificial liver (SRBAL) was evaluated in a porcine model of drug-overdose acute liver failure (ALF). METHODS: Healthy pigs were randomized into three groups (standard therapy (ST) alone, ST+No-cell device, ST+SRBAL device) before placement of an implantable intracranial pressure (ICP) monitor and a tunneled central venous catheter. One week later, pigs received bolus infusion of the hepatotoxin D-galactosamine and were followed for up to 90h. RESULTS: At 48h, all animals had developed encephalopathy and biochemical changes confirming ALF; extracorporeal treatment was initiated and pigs were observed up to 90h after drug infusion. Pigs treated with the SRBAL, loaded with porcine hepatocyte spheroids, had improved survival (83%, n=6) compared to ST alone (0%, n=6, p=0.003) and No-cell device therapy (17%, n=6, p=0.02). Ammonia detoxification, peak levels of serum ammonia and peak ICP, and pig survival were influenced by hepatocyte cell dose, membrane pore size and duration of SRBAL treatment. Hepatocyte spheroids remained highly functional with no decline in mean oxygen consumption from initiation to completion of treatment. CONCLUSIONS: The SRBAL improved survival in an allogeneic model of drug-overdose ALF. Survival correlated with ammonia detoxification and ICP lowering indicating that hepatocyte spheroids prevented the cerebral manifestations of ALF (brain swelling, herniation, death). Further investigation of SRBAL therapy in a clinical setting is warranted.
BACKGROUND & AIMS: The neuroprotective effect of the spheroid reservoir bioartificial liver (SRBAL) was evaluated in a porcine model of drug-overdose acute liver failure (ALF). METHODS: Healthy pigs were randomized into three groups (standard therapy (ST) alone, ST+No-cell device, ST+SRBAL device) before placement of an implantable intracranial pressure (ICP) monitor and a tunneled central venous catheter. One week later, pigs received bolus infusion of the hepatotoxin D-galactosamine and were followed for up to 90h. RESULTS: At 48h, all animals had developed encephalopathy and biochemical changes confirming ALF; extracorporeal treatment was initiated and pigs were observed up to 90h after drug infusion. Pigs treated with the SRBAL, loaded with porcine hepatocyte spheroids, had improved survival (83%, n=6) compared to ST alone (0%, n=6, p=0.003) and No-cell device therapy (17%, n=6, p=0.02). Ammonia detoxification, peak levels of serum ammonia and peak ICP, and pig survival were influenced by hepatocyte cell dose, membrane pore size and duration of SRBAL treatment. Hepatocyte spheroids remained highly functional with no decline in mean oxygen consumption from initiation to completion of treatment. CONCLUSIONS: The SRBAL improved survival in an allogeneic model of drug-overdose ALF. Survival correlated with ammonia detoxification and ICP lowering indicating that hepatocyte spheroids prevented the cerebral manifestations of ALF (brain swelling, herniation, death). Further investigation of SRBAL therapy in a clinical setting is warranted.
Authors: Scott L Nyberg; Toshikazu Yagi; Takakazu Matsushita; Joseph Hardin; Joseph P Grande; Lawrence E Gibson; Jeffrey L Platt Journal: Liver Transpl Date: 2003-03 Impact factor: 5.799
Authors: E Morsiani; P Pazzi; A C Puviani; M Brogli; L Valieri; P Gorini; P Scoletta; E Marangoni; R Ragazzi; G Azzena; E Frazzoli; D Di Luca; E Cassai; G Lombardi; A Cavallari; S Faenza; A Pasetto; M Girardis; E Jovine; A D Pinna Journal: Int J Artif Organs Date: 2002-03 Impact factor: 1.595
Authors: I M Sauer; K Zeilinger; N Obermayer; G Pless; A Grünwald; A Pascher; T Mieder; S Roth; M Goetz; D Kardassis; A Mas; P Neuhaus; J C Gerlach Journal: Int J Artif Organs Date: 2002-10 Impact factor: 1.595
Authors: Achilles A Demetriou; Robert S Brown; Ronald W Busuttil; Jeffrey Fair; Brendan M McGuire; Philip Rosenthal; Jan Schulte Am Esch; Jan Lerut; Scott L Nyberg; Mauro Salizzoni; Elizabeth A Fagan; Bernard de Hemptinne; Christoph E Broelsch; Maurizio Muraca; Joan Manuel Salmeron; John M Rabkin; Herold J Metselaar; Daniel Pratt; Manuel De La Mata; Lawrence P McChesney; Gregory T Everson; Philip T Lavin; Anthony C Stevens; Zorina Pitkin; Barry A Solomon Journal: Ann Surg Date: 2004-05 Impact factor: 12.969
Authors: I M Sauer; D Kardassis; K Zeillinger; A Pascher; A Gruenwald; G Pless; M Irgang; M Kraemer; G Puhl; J Frank; A R Müller; T Steinmüller; J Denner; P Neuhaus; J C Gerlach Journal: Xenotransplantation Date: 2003-09 Impact factor: 3.907
Authors: Takakazu Matsushita; Bruce Amiot; Joseph Hardin; Jeffrey L Platt; Scott L Nyberg Journal: Transplantation Date: 2003-11-15 Impact factor: 4.939
Authors: Clara T Nicolas; Raymond D Hickey; Harvey S Chen; Shennen A Mao; Manuela Lopera Higuita; Yujia Wang; Scott L Nyberg Journal: Stem Cells Date: 2016-10-02 Impact factor: 6.277
Authors: Harvey S Chen; Dong Jin Joo; Mohammed Shaheen; Yi Li; Yujia Wang; Jian Yang; Clara T Nicolas; Kelly Predmore; Bruce Amiot; Gregory Michalak; Taofic Mounajjed; Jeff Fidler; Walter K Kremers; Scott L Nyberg Journal: Hepatology Date: 2018-12-27 Impact factor: 17.425
Authors: Victor Dong; Maxime Gosselin; Nishita Jagarlamudi; Beverley Kok; Mark G Swain; Jasmohan S Bajaj; Juan G Abraldes; Vladimir Marquez; R Todd Stravitz; Aldo J Montano-Loza; Manuela Merli; Phil Wong; Amanda Brisebois; Puneeta Tandon; Julia Wendon; Scott L Nyberg; François M Carrier; Michael R Lucey; Florence Wong; Jordan J Feld; Constantine J Karvellas; Christopher F Rose; Julien Bissonnette Journal: Can Liver J Date: 2019-12-10
Authors: Lei Cai; Jun Weng; Lei Feng; Guolin He; Jiasheng Qin; Zhi Zhang; Yang Li; Qing Peng; Zesheng Jiang; Mingxin Pan; Yi Gao Journal: Biomed Res Int Date: 2016-12-21 Impact factor: 3.411
Authors: Martien van Wenum; Aziza A A Adam; Theodorus B M Hakvoort; Erik J Hendriks; Valery Shevchenko; Thomas M van Gulik; Robert A F M Chamuleau; Ruurdtje Hoekstra Journal: Int J Biol Sci Date: 2016-06-24 Impact factor: 6.580