Perfusion cell seeding and cultivation induce the assembly of thick and functional hepatocellular tissue-like construct

Irena Shvartsman, Tal Dvir, Tamar Harel-Adar, Smadar Cohen

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Developing advanced technologies for encouraging the ex vivo assembly of functional hepatic tissue for implantation into the human body or for in vitro drug testing is one of the challenging tasks facing tissue engineers. In the present study, we utilized a perfusion bioreactor system equipped with a novel flow-distributing mesh for online cell seeding into macroporous alginate scaffolds and cultivation of multiple constructs of the C3A human hepatocyte cell line. Optimization of the medium flow rate (100 mL/min) and perfusion duration (12 h) yielded cell constructs with high cell seeding efficiency (98% of the input cells) and cell distribution throughout the entire scaffold. Further, we show that interstitial medium flow enabled uniform cell delivery into 35 constructs lined across the bioreactor cross section. Perfusion-cultivated cell constructs revealed much greater rates of cell proliferation, albumin-specific secretion, and gene expression of the phase I enzyme, CYP3A4, and phase II enzyme, UGT2B7, than did static-cultivated constructs. Most impressive was the 50-fold increase in CYP3A4 expression of the perfused cell constructs as compared to the level in static-cultivated cell constructs. We thus believe that the hepatic tissue constructs developed herein may be used in drug discovery programs for elucidating drug metabolism and toxicity profiles and for treating failing livers.

Original languageEnglish
Pages (from-to)751-760
Number of pages10
JournalTissue Engineering - Part A.
Volume15
Issue number4
DOIs
StatePublished - 1 Apr 2009

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Fingerprint

Dive into the research topics of 'Perfusion cell seeding and cultivation induce the assembly of thick and functional hepatocellular tissue-like construct'. Together they form a unique fingerprint.

Cite this