Hepatic Differentiation of Mouse Embryonic Stem Cells in a Bioreactor Using Polyurethane/Spheroid Culture

K. Matsumoto, Hiroshi Mizumoto, K. Nakazawa, Hiroyuki Ijima, K. Funatsu, Toshihisa Kajiwara

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Background: We have previously developed a hybrid artificial liver (HAL) using polyurethane foam (PUF)/hepatocyte spheroid culture. The PUF-HAL has been successfully scaled up to a clinical level. However, one of the most difficult problems for clinical application of HALs is obtaining a cell source. We now focused our attention on embryonic stem (ES) cells as a potential source for HAL. In this study, we investigated the differentiation of mouse ES (mES) cells into functional hepatocytes in the PUF-HAL module. Methods: The PUF-HAL module included a cylindrical PUF block having many capillaries for medium flow. mES cells were immobilized in the module. To induce hepatic differentiation, growth factors were added to the culture medium. We evaluated cell density, gene expression analysis, and liver-specific functions. Results: mES cells spontaneously formed spherical multicellular aggregates (spheroids) in the pores of PUF. mES cells proliferated by 20 days, achieving a high cell density (about 1 × 108 cells/cm3 PUF). Differentiating ES cells expressed endodermal-specific genes such as α-fetoprotein, albumin, and tryptophan 2, 3-deoxygenase. The activity of ammonia removal of mES cells per unit volume of the module was detectable by 15 days and increased with culture time. Maximal expression levels were comparable to those of primary (porcine and human) hepatocytes. Summary: mES cells immobilized in the PUF module expressed liver-specific functions at high level, because of high cell density in culture and hepatic differentiation. These results indicated that PUF module-immobilized mES cells may be useful as a biocomponent of HALs.

Original languageEnglish
Pages (from-to)614-616
Number of pages3
JournalTransplantation Proceedings
Volume40
Issue number2
DOIs
Publication statusPublished - Mar 1 2008

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

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