Therapeutic potential of human adipose tissue-derived multi-lineage progenitor cells in liver fibrosis.

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.
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.
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.
AuthorsHanayuki Okura, Mayumi Soeda, Mitsuko Morita, Maiko Fujita, Kyoko Naba, Chiyoko Ito, Akihiro Ichinose, Akifumi Matsuyama
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 456 Issue 4 Pg. 860-5 (Jan 24 2015) ISSN: 1090-2104 [Electronic] United States
PMID25490388 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Carbon Tetrachloride
  • Matrix Metalloproteinases
  • Adipose Tissue (cytology)
  • Adult
  • Animals
  • Carbon Tetrachloride
  • Cell Lineage
  • Female
  • Humans
  • Liver Cirrhosis (blood, pathology, physiopathology, therapy)
  • Liver Function Tests
  • Matrix Metalloproteinases (metabolism)
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stromal Cells (cytology, enzymology)
  • Mice, Nude
  • Middle Aged
  • Recovery of Function
  • Young Adult

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