title: Therapeutic potential of human adipose tissue-derived multi-lineage progenitor cells in liver fibrosis.
abstract: BACKGROUND
  Liver fibrosis is characterized by excessive accumulation of extracellular matrix. In a mouse model of liver fibrosis, systemic injection of bone marrow mesenchymal stem cells (BM-MSCs) was considered to rescue the diseased phenotype. The aim of this study was to assess the effectiveness of human adipose tissue-derived multi-lineage progenitor cells (hADMPCs) in improving liver fibrosis.
  
  
  RESULTS
  hADMPCs were isolated from subcutaneous adipose tissues of healthy volunteers and expanded. Six week-old male nude mice were treated with carbon tetra-chloride (CCl4) by intraperitoneal injection twice a week for 6 weeks, followed by a tail vein injection of hADMPCs or placebo control. After 6 more weeks of CCl4 injection (12 weeks in all), nude mice with hADMPCs transplants exhibited a significant reduction in liver fibrosis, as evidenced by Sirius Red staining, compared with nude mice treated with CCl4 for 12 weeks without hADMPCs transplants. Moreover, serum glutamic pyruvate transaminase and total bilirubin levels in hADMPCs-treated nude mice were lower levels than those in placebo controls. Production of fibrinolytic enzyme MMPs from hADMPCs were examined by ELISA and compared to that from BM-MSCs. MMP-2 levels in the culture media were not significantly different, whereas those of MMP-3 and -9 of hADMPCs were higher than those by BM-MSCs.
  
  
  CONCLUSIONS
  These results showed the mode of action and proof of concept of systemic injection of hADMPCs, which is a promising therapeutic intervention for the treatment of patients with liver fibrosis.
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 5-5-2-602 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879, Japan.
authors.forename: Hanayuki
authors.initials: H
authors.lastname: Okura
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 5-5-2-602 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Soeda
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 5-5-2-602 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Morita
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 5-5-2-602 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Fujita
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 5-5-2-602 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Naba
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 5-5-2-602 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Ito
authors.affiliation: Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ichinose
authors.affiliation: Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, 5-5-2-602 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879, Japan. Electronic address: akifumi-matsuyama@umin.ac.jp.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Matsuyama
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D002251:Carbon Tetrachloride; D019070:Cell Lineage; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008111:Liver Function Tests; D020782:Matrix Metalloproteinases / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000201:enzymology; D008819:Mice, Nude; D008875:Middle Aged; D020127:Recovery of Function; D055815:Young Adult
chemical_list: D002251:Carbon Tetrachloride; D020782:Matrix Metalloproteinases
keywords: Chronic hepatitis; Fibrosis; MMPs; Mouse; hADMPCs