Properties of hepatocyte-like cell clusters from human adipose tissue-derived mesenchymal stem cells

Hanayuki Okura, Hiroshi Komoda, Ayami Saga, Aya Kakuta-Yamamoto, Yoko Hamada, Yuichi Fumimoto, Chun Man Lee, Akihiro Ichinose, Yoshiki Sawa, Akifumi Matsuyama

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

There are only a few reports that describe the hepatocytic differentiation potential of human adipose tissue-derived mesenchymal stem cells (hADMSCs) and no reports that describe the in vivo functions of hepatocyte-like cells differentiated from somatic stem cells including hADMSCs. In this study, we established a new method for generation of functional hepatocyte-like cell clusters using floating culture method and induced functional hepatocyte-like cell clusters, which functioned effectively not only in vitro but also in vivo. The generated hepatocyte-like cell clusters were characterized by gene expression analysis, functional assays, and transplantation into non-obese diabetic severe combined immunodeficiency (NOD-SCID) mouse with chronic liver injury. The generated hepatocyte-like cell clusters expressed various genes normally found on mature hepatocytes. The cell clusters exhibited functional characteristics of hepatocytes: they expressed albumin, secreted urea, had cytochrome P450 activity, could take up low-density lipoprotein, and stored glycogen. Transplantation of these cell clusters into NOD-SCID mouse with chronic liver injury resulted in a significant improvement of serum albumin and total bilirubin levels. In summary, we established a new protocol for efficient induction of hADMSCs into functional hepatocyte-like cell clusters.

Original languageEnglish
Pages (from-to)761-770
Number of pages10
JournalTissue Engineering - Part C: Methods
Volume16
Issue number4
DOIs
Publication statusPublished - 01-08-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Bioengineering
  • Biomedical Engineering

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