Document Detail

Time course of primary liver cell reorganization in three-dimensional high-density bioreactors for extracorporeal liver support: an immunohistochemical and ultrastructural study.
MedLine Citation:
PMID:  15363168     Owner:  NLM     Status:  MEDLINE    
To enable extracorporeal liver support based on the use of primary liver cells, culture models supporting the maintenance of cell integrity and function in vitro are required. In this study the cell organization and ultrastructure of primary porcine hepatocytes cocultured with nonparenchymal cells in three-dimensional high-density bioreactors were analyzed after 10, 20, and 30 days of culture by immunohistochemistry and transmission electron microscopy. Biochemical data showed that metabolic activity of the cells in the system was relatively stable over at least 20 days. Immunohistochemical studies were performed in comparison with donor organ biopsies. They showed that hepatocytes and nonparenchymal cells reaggregated in bioreactors, forming structures partly resembling natural liver parenchyma. Bile duct-like structures characterized by cytokeratin 7 (CK-7) immunoreactivity (IR) were regularly detected. Nonparenchymal cells (vimentin IR) formed sinusoidal-like structures within parenchymal cell aggregates. Proliferative activity (Ki-67 IR) increased over time. The detection of collagen I and laminin indicated the production of extracellular matrix components within bioreactors. The results showed that primary liver cell reorganization and long-term maintenance of their differentiated state were achieved within the bioreactors The findings on cell proliferation indicated that the culture model is also of interest for further in vitro studies on cell regeneration and tissue formation.
Katrin Zeilinger; Gudrun Holland; Igor M Sauer; Ekaterina Efimova; Dimitrios Kardassis; Nicole Obermayer; Marcus Liu; Peter Neuhaus; Jörg C Gerlach
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Tissue engineering     Volume:  10     ISSN:  1076-3279     ISO Abbreviation:  Tissue Eng.     Publication Date:    2004 Jul-Aug
Date Detail:
Created Date:  2004-09-14     Completed Date:  2005-03-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9505538     Medline TA:  Tissue Eng     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1113-24     Citation Subset:  IM    
Department of Experimental Surgery, Surgical Clinic, Charité Campus Virchow, University Medicine, 11353 Berlin, Germany.
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MeSH Terms
Adaptation, Physiological / physiology
Cell Culture Techniques / instrumentation,  methods
Cell Proliferation
Cells, Cultured
Coculture Techniques / methods*
Extracellular Matrix Proteins / metabolism*
Hepatocytes / metabolism*,  ultrastructure*
Keratins / metabolism*
Liver, Artificial*
Time Factors
Tissue Engineering / methods*
Reg. No./Substance:
0/Extracellular Matrix Proteins; 68238-35-7/Keratins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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