Liver tissue engineering: a role for co-culture systems in modifying hepatocyte function and viability.
A major limitation in the construction of a functional engineered liver is the short-term survival and rapid de-differentiation of hepatocytes in culture. Heterotypic cell-cell interactions may have a role to play in modulating long-term hepatocyte behavior in engineered tissues. We describe the potential of 3T3 fibroblast cells in a co-culture system to modulate function and viability of primary isolated rat hepatocytes. Over an 18-day period after isolation, hepatocytes in pure culture rapidly declined in viability, displayed sparse bile canaliculi, and lost two function markers, the secretion of albumin and ethoxyresorufin O-dealkylase (EROD) activity. In comparison, the hepatocytes within the co-cultures maintained viability, possessed well-formed canalicular systems, and displayed both functional markers. Fixed 3T3 cells or 3T3 cell conditioned medium did not substitute for the viable 3T3 cell co-culture system in preserving hepatocyte viability and functionality.
Bhandari
R N
RN
School of Pharmaceutical Sciences, The University of Nottingham, Nottingham, NG7 2RD, UK.
Riccalton
L A
LA
Lewis
A L
AL
Fry
J R
JR
Hammond
A H
AH
Tendler
S J
SJ
Shakesheff
K M
KM
D016475:3T3 Cells; D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001698:Biomedical Engineering; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D022781:Hepatocytes / Q000276:immunology / Q000502:physiology*; D007150:Immunohistochemistry; D007633:Keratins / Q000276:immunology; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000418:Albumins; D017077:Culture Media, Conditioned; D007633:Keratins; D019363:Cytochrome P-450 CYP1A1