Hepatic tissue engineering on 3-dimensional biodegradable polymers within a pulsatile flow bioreactor.
BACKGROUND
An optimal method for hepatocyte transplantation is not yet determined. With the principles of tissue engineering in vitro conditioning of hepatocytes on biodegradable polymer in a flow bioreactor before implantation forming spheroids may achieve increased cell mass and function to replace lost organ function in vivo.


METHODS
Biodegradable poly-L-lactic (PLLA) polymer discs were seeded with rat hepatocytes in a concentration of 10 x 10(6) cells per ml and exposed to a medium flow of 24 ml/min for 1, 2, 4 and 6 days. The number and diameter of spheroidal aggregates was measured by phase-contrast microscopy. H&E histology was performed. Albumin production as hepatocyte specific function was determined by ELISA.


RESULTS
Spheroids of viable hepatocytes of 50-200 microm in diameter were formed. Both the number and diameter of the spheroids increased during the first 2 days and then remained constant until day 6. Albumin production was maintained throughout the culture period.


CONCLUSIONS
Short (2- 3 days) pre-transplant conditioning of hepatocytes in a flow bioreactor on biodegradable PLLA resulted in formation of spheroids with a liver-like morphology and preserved specific metabolic function. Tissue engineered hepatocyte spheroids on polymer may represent a functionally active and easy transplantable neotissue and may serve as an in vivo substitute for lost liver function.
Török E
Department of Hepatobiliary Surgery, University of Hamburg, Germany. toeroek@uke.uni-hamburg.de
Pollok
J M
JM
Ma
P X
PX
Vogel
C
C
Dandri
M
M
Petersen
J
J
Burda
M R
MR
Kaufmann
P M
PM
Kluth
D
D
Rogiers
X
X
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials; D001698:Biomedical Engineering / Q000295:instrumentation / Q000379:methods*; D019149:Bioreactors; D017690:Cell Transplantation / Q000379:methods; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D016031:Liver Transplantation; D011108:Polymers; D011673:Pulsatile Flow; D051381:Rats; D011917:Rats, Inbred Lew; D018874:Spheroids, Cellular / Q000378:metabolism / Q000637:transplantation*; D013997:Time Factors
D000418:Albumins; D001672:Biocompatible Materials; D011108:Polymers; D019344:Lactic Acid