Use of ultrathin shell microcapsules of hepatocytes in bioartificial liver-assist device

Tao Sun, Melinda L.H. Chan, Yi Zhou, Xi Xu, Jing Zhang, Xuejun Lao, Xianwei Wang, Chai Hoon Quek, Jia Ping Chen, Kam W. Leong, Hanry Yu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

We previously encapsulated hepatocytes in ultrathin shell microcapsules and showed them to have enhanced differentiated functions over cells cultured in monolayer. Here we have used these microencapsulated hepatocytes in a bioartificial liver-assisted device (BLAD) with a rat hepatectomy model. Primary rat hepatocytes were encapsulated in 150- to 200-μm microcapsules, using an electrostatic droplet generator. The microencapsulated hepatocytes exhibited good in vitro urea synthesis activity in plasma from rats with fulminant hepatic failure (FHF). The ex vivo hemoperfusion was conducted in FHF rats by perfusing plasma at a rate of 1-2 mL/min through 1.5-2 × 10 8 encapsulated hepatocytes packed into a packed-bed bioreactor. Hemoperfusion with the bioreactor was initiated 5 h after operative induction of liver failure and continued for 7 h. The BLAD-treated rats showed improvements over the control groups in survival time and metabolic indicators, including ammonia and total bilirubin levels. Furthermore, expanded bed adsorption (EBA) detoxification technology using Streamline-SP resin was explored to complement the bioreactor with microencapsulated hepatocytes. In vitro experiments indicated that serum ammonia could be specifically removed in dose-dependent manner, whereas the total serum proteins were unaffected by the resin. In ex vivo experiments, hemoperfusion with the resin was initiated 3 h after operative induction of liver failure and continued for 7 h. The resin-treated rats showed obvious serum ammonia removal with no observable total blood protein and blood cell adsorption. Therefore, Streamline-SP resin can potentially be integrated into a BLAD for improved efficacy.

Original languageEnglish
Pages (from-to)S65-S75
JournalTissue Engineering
Volume9
Issue numberSUPPL. 1
DOIs
StatePublished - 2003
Externally publishedYes

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