TY - JOUR
T1 - Therapeutic potential of human adipose tissue-derived multi-lineage progenitor cells in liver fibrosis
AU - Okura, Hanayuki
AU - Soeda, Mayumi
AU - Morita, Mitsuko
AU - Fujita, Maiko
AU - Naba, Kyoko
AU - Ito, Chiyoko
AU - Ichinose, Akihiro
AU - Matsuyama, Akifumi
N1 - Funding Information:
This study was partly supported by a grant-in-aid for A.M. from the Ministry of Health, Labor and Welfare , Japan.
PY - 2015/1/24
Y1 - 2015/1/24
N2 - Introduction: 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. Methods and 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. Conclusion: 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.
AB - Introduction: 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. Methods and 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. Conclusion: 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.
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U2 - 10.1016/j.bbrc.2014.11.122
DO - 10.1016/j.bbrc.2014.11.122
M3 - Article
C2 - 25490388
AN - SCOPUS:84921269587
VL - 456
SP - 860
EP - 865
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -