Properties of Hepatocyte-like Cell Clusters from Human Adipose Tissue-Derived Mesenchymal Stem Cells

• Published in: Tissue engineering. Part C, Methods Vol. 16; no. 4; pp. 761 - 770
• Main Authors: Okura, Hanayuki, Komoda, Hiroshi, Saga, Ayami, Kakuta-Yamamoto, Aya, Hamada, Yoko, Fumimoto, Yuichi, Lee, Chun Man, Ichinose, Akihiro, Sawa, Yoshiki, Matsuyama, Akifumi
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.08.2010
• Subjects: Adipose Tissue - cytology; Adipose tissues; Adult; Animals; Body fat; Cell Aggregation; Cell Differentiation; Cell Line, Tumor; Cells; Female; Gene expression; Gene Expression Regulation; Genetic aspects; Growth; Hepatocytes - cytology; Hepatocytes - transplantation; Humans; Liver cells; Liver Diseases - therapy; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mice; Mice, SCID; Middle Aged; Physiological aspects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stem cells; Tissues; Japan
• ISSN: 1937-3384; 1937-3392
• DOI: 10.1089/ten.tec.2009.0208

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.