Scaling down of a clinical three-dimensional perfusion multicompartment hollow fiber liver bioreactor developed for extracorporeal liver support to an analytical scale device useful for hepatic pharmacological in vitro studies.
Tissue Eng Part C Methods
; 17(5): 549-56, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21210724
ABSTRACT
Within the scope of developing an in vitro culture model for pharmacological research on human liver functions, a three-dimensional multicompartment hollow fiber bioreactor proven to function as a clinical extracorporeal liver support system was scaled down in two steps from 800 mL to 8 mL and 2 mL bioreactors. Primary human liver cells cultured over 14 days in 800, 8, or 2 mL bioreactors exhibited comparable time-course profiles for most of the metabolic parameters in the different bioreactor size variants. Major drug-metabolizing cytochrome P450 activities analyzed in the 2 mL bioreactor were preserved over up to 23 days. Immunohistochemical studies revealed tissue-like structures of parenchymal and nonparenchymal cells in the miniaturized bioreactor, indicating physiological reorganization of the cells. Moreover, the canalicular transporters multidrug-resistance-associated protein 2, multidrug-resistance protein 1 (P-glycoprotein), and breast cancer resistance protein showed a similar distribution pattern to that found in human liver tissue. In conclusion, the down-scaled multicompartment hollow fiber technology allows stable maintenance of primary human liver cells and provides an innovative tool for pharmacological and kinetic studies of hepatic functions with small cell numbers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Perfusão
/
Técnicas de Cultura de Células
/
Reatores Biológicos
/
Fígado Artificial
/
Engenharia Tecidual
/
Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Tissue Eng Part C Methods
Assunto da revista:
BIOTECNOLOGIA
/
HISTOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Alemanha