15. Bioartificial extracorporeal liver support: The need for hypothermic hypometabolic long-term culture of primary human liver cells in perfusion bioreactors

Cryobiology ◽  
2006 ◽  
Vol 53 (3) ◽  
pp. 373
Author(s):  
Igor M. Sauer
Keyword(s):  
Human Liver ◽  
Liver Cells ◽  
Liver Support ◽  
Long Term Culture ◽  
Human Liver Cells ◽  
Extracorporeal Liver Support ◽  
Perfusion Bioreactors

Primary Human Liver Cells as Source for Modular Extracorporeal Liver Support - a Preliminary Report

2002 ◽  
Vol 25 (10) ◽  
pp. 1001-1005 ◽  
Author(s):  
I.M. Sauer ◽  
K. Zeilinger ◽  
N. Obermayer ◽  
G. Pless ◽  
A. Grünwald ◽  
...  
Keyword(s):  
Human Liver ◽  
Treatment Time ◽  
Liver Perfusion ◽  
Cell Mass ◽  
Liver Weight ◽  
Liver Cells ◽  
Liver Support ◽  
Overall Treatment Time ◽  
Human Liver Cells ◽  
Extracorporeal Liver Support

Cell-based extracorporeal liver support is an option to assist or replace the failing organ until regeneration or until transplantation can be performed. The use of porcine cells or tumor cell lines is controversial. Primary human liver cells, obtained from explanted organs found to be unsuitable for transplantation, are a desirable cell source as they perform human metabolism and regulation. The Modular Extracorporeal Liver Support (MELS) concept combines different extracorporeal therapy units, tailored to suit the individual and intra-individual clinical needs of the patient. A multi-compartment bioreactor (CellModule) is loaded with human liver cells obtained by 5-step collagenase liver perfusion. A cell mass of 400 g – 600 g enables the clinical application of a liver lobe equivalent hybrid organ. A detoxification module enables single pass albumin-dialysis via a standard high-flux dialysis filter, and continuous venovenuous hemodiafiltration may be included if required. Cells from 54 human livers have been isolated (donor age: 56 ± 13 years, liver weight: 1862 ± 556 g resulting in a viability of 55.0 ± 15.9%). These grafts were not suitable for LTx, due to steatosis (54%), cirrhosis (15%), fibrosis (9%), and other reasons (22%). Out of 36 prepared bioreactors, 10 were clinically used to treat 8 patients with liver failure. The overall treatment time was 7–144 hours. No adverse events were observed. Initial clinical applications of the bioreactor evidenced the technical feasibility and safety of the system.

Extracorporeal liver support based on primary human liver cells and albumin dialysis – treatment of a patient with primary graft non-function

2003 ◽  
Vol 39 (4) ◽  
pp. 649-653 ◽  
Author(s):  
Igor M. Sauer ◽  
Katrin Zeilinger ◽  
Gesine Pless ◽  
Dimitrios Kardassis ◽  
Tom Theruvath ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Cells ◽  
Albumin Dialysis ◽  
Liver Support ◽  
Dialysis Treatment ◽  
Human Liver Cells ◽  
Extracorporeal Liver Support

Evaluation of Primary Human Liver Cells in Bioreactor Cultures for Extracorporeal Liver Support on the Basis of Urea Production

2006 ◽  
Vol 30 (9) ◽  
pp. 686-694 ◽  
Author(s):  
Gesine Pless ◽  
Ingo Steffen ◽  
Katrin Zeilinger ◽  
Igor M. Sauer ◽  
Ekaterina Katenz ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Cells ◽  
Liver Support ◽  
Human Liver Cells ◽  
Bioreactor Cultures ◽  
Extracorporeal Liver Support ◽  
Urea Production

HUMAN LIVER CELLS IN A 3-D HIGH DENSITY FOUR-COMPARTMENT COCULTURE BIOREACTOR FOR A MODULAR EXTRACORPOREAL LIVER SUPPORT CONCEPT

ASAIO Journal ◽  
2003 ◽  
Vol 49 (2) ◽  
pp. 205
Author(s):  
J. C. Gerlach ◽  
I. M. Sauer ◽  
K. Zeilinger ◽  
G. Pless ◽  
D. Borzelleca ◽  
...  
Keyword(s):  
Human Liver ◽  
Liver Cells ◽  
High Density ◽  
Liver Support ◽  
Human Liver Cells ◽  
Extracorporeal Liver Support

Three-dimensional Co-culture of Primary Human Liver Cells in Bioreactors for In Vitro Drug Studies: Effects of the Initial Cell Quality on the Long-term Maintenance of Hepatocyte-specific Functions

2002 ◽  
Vol 30 (5) ◽  
pp. 525-538 ◽  
Author(s):  
Katrin Zeilinger ◽  
Igor M. Sauer ◽  
Gesine Pless ◽  
Catrin Strobel ◽  
Jeannette Rudzitis ◽  
...  
Keyword(s):  
Pharmaceutical Industry ◽  
Human Liver ◽  
Three Dimensional ◽  
Liver Cells ◽  
Bioreactor Culture ◽  
Initial Cell ◽  
Human Liver Cells ◽  
Term Maintenance

In vitro culture models that employ human liver cells could be potent tools for predictive studies on drug toxicity and metabolism in the pharmaceutical industry. A bioreactor culture model was developed that permits the three-dimensional co-culture of liver cells under continuous medium perfusion with decentralised mass exchange and integral oxygenation. We tested the ability of the system to support the long-term maintenance and differentiation of primary human liver cells. The effects of the initial cell quality were investigated by comparing cultures from resected, non-preserved liver with cultures from liver graft tissue damaged by long-term preservation. In cultures originating from non-preserved liver, protein and urea synthesis, glucose metabolism, and cytochrome (P450) activities were stable over the 2-week culture period, with maximal activities at the end of the first week in culture. Enzyme induction led to increased 7-ethoxyresorufin O-deethylase activities of up to 20 times the basal value. In cultures from preservation-damaged liver, recovery of metabolic activities was detected during bioreactor culture. After two weeks, most biochemical parameters approached those of cultures from non-preserved human liver. Light microscopy demonstrated the three-dimensional reorganisation of hepatocytes and nonparenchymal cells in co-culture. Long-term maintenance, and even the regeneration of specific functional activities of human liver cells, can be achieved in the bioreactor. This could facilitate the introduction into the pharmaceutical industry of in vitro drug testing with primary human liver cells.

PRIMARY HUMAN LIVER CELLS ISOLATED FROM TRANSPLANT DISCARDS USED IN A HYBRID LIVER SUPPORT SYSTEM

ASAIO Journal ◽  
2001 ◽  
Vol 47 (2) ◽  
pp. 174
Author(s):  
Goetz Naumann ◽  
Dimitrios Kardassis ◽  
Nicole Obermayer ◽  
Igor M. Sauer ◽  
Esteve Trias ◽  
...  
Keyword(s):  
Support System ◽  
Human Liver ◽  
Liver Cells ◽  
Liver Support ◽  
Human Liver Cells ◽  
Liver Support System
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