Properties of hepatocyte-like cell clusters from human adipose tissue-derived mesenchymal stem cells.
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.
Department of Somatic Stem Cell Therapy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe, Japan.
Hanayuki
H
Okura
Hiroshi
H
Komoda
Ayami
A
Saga
Aya
A
Kakuta-Yamamoto
Yoko
Y
Hamada
Yuichi
Y
Fumimoto
Chun Man
CM
Lee
Akihiro
A
Ichinose
Yoshiki
Y
Sawa
Akifumi
A
Matsuyama
D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D002449:Cell Aggregation; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000166:cytology* / Q000637:transplantation; D006801:Humans; D008107:Liver Diseases / Q000628:therapy; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger