Bioengineering of a CLiP-derived tubular biliary-duct-like structure for bile transport in vitro.
Biotechnol Bioeng
; 118(7): 2572-2584, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-33811654
ABSTRACT
The integration of a bile drainage structure into engineered liver tissues is an important issue in the advancement of liver regenerative medicine. Primary biliary cells, which play a vital role in bile metabolite accumulation, are challenging to obtain in vitro because of their low density in the liver. In contrast, large amounts of purified hepatocytes can be easily acquired from rodents. The in vitro chemically induced liver progenitors (CLiPs) from primary mature hepatocytes offer a platform to produce biliary cells abundantly. Here, we generated a functional CLiP-derived tubular bile duct-like structure using the chemical conversion technology. We obtained an integrated tubule-hepatocyte tissue via the direct coculture of hepatocytes on the established tubular biliary-duct-like structure. This integrated tubule-hepatocyte tissue was able to transport the bile, as quantified by the cholyl-lysyl-fluorescein assay, which was not observed in the un-cocultured structure or in the biliary cell monolayer. Furthermore, this in vitro integrated tubule-hepatocyte tissue exhibited an upregulation of hepatic marker genes. Together, these findings demonstrated the efficiency of the CLiP-derived tubular biliary-duct-like structures regarding the accumulation and transport of bile.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Bile
/
Sistema Biliar
/
Diferenciação Celular
/
Hepatócitos
/
Células Epiteliais
Limite:
Animals
Idioma:
En
Revista:
Biotechnol Bioeng
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Japão