Extended liver-specific functions of porcine hepatocyte spheroids entrapped in collagen gel

Arye Lazar, Henry J. Mann, Rory P. Remmel, Russell A. Shatford, Frank B. Cerra, Wei Shou Hu

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The potential use of porcine hepatocytes in a bioartificial liver device requires large quantities of viable and highly active cells. To facilitate the scaling up of the system, liver specific activities of hepatocytes should be maximized. One way of enhancing the specific activities is to cultivate hepatocytes as multicellular spheroids. Freshly isolated porcine hepatocytes form spheroids when cultivated in suspended cultures. These spheroids exhibit higher activities for a number of liver specific functions compared to hepatocytes cultivated as monolayers. However, these activities decreased in a few days in culture. Entrappment of spheroids in collagen gel sustained their metabolic activities at a stable level over 21 days. Production of albumin and urea by spheroid hepatocytes entrapped in collagen gels were 2 to 3 times higher than those by freshly isolated single cells. P-450 activity was demonstrated by metabolism of lidocaine to its main metabolite, monoethylglycinexylidide. Phase II drug metabolism was demonstrated by glucuronidation of 4-methylumbelliferone. This work shows that porcine hepatocyte spheroids entrapped in collagen maintain differentiated functions for an extended time period. Such hepatocyte spheroid entrappment system may facilitate the development of a bioartificial liver support device.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalIn Vitro Cellular & Developmental Biology - Animal
Volume31
Issue number5
DOIs
StatePublished - May 1 1995

Keywords

  • P-450
  • artificial liver
  • glucuronidation
  • porcine hepatocyte
  • spheroids

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