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

Hanayuki Okura, Mayumi Soeda, Mitsuko Morita, Maiko Fujita, Kyoko Naba, Chiyoko Ito, Akihiro Ichinose, Akifumi Matsuyama

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)860-865
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume456
Issue number4
DOIs
Publication statusPublished - 24-01-2015

Fingerprint

Liver Cirrhosis
Liver
Adipose Tissue
Stem Cells
Tissue
Nude Mice
Matrix Metalloproteinases
Mesenchymal Stromal Cells
Stem cells
Injections
Therapeutics
Bone Marrow
Transplants
Bone
Placebos
Subcutaneous Fat
Transaminases
Intraperitoneal Injections
Pyruvic Acid
Bilirubin

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Okura, Hanayuki ; Soeda, Mayumi ; Morita, Mitsuko ; Fujita, Maiko ; Naba, Kyoko ; Ito, Chiyoko ; Ichinose, Akihiro ; Matsuyama, Akifumi. / Therapeutic potential of human adipose tissue-derived multi-lineage progenitor cells in liver fibrosis. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 456, No. 4. pp. 860-865.
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Therapeutic potential of human adipose tissue-derived multi-lineage progenitor cells in liver fibrosis. / Okura, Hanayuki; Soeda, Mayumi; Morita, Mitsuko; Fujita, Maiko; Naba, Kyoko; Ito, Chiyoko; Ichinose, Akihiro; Matsuyama, Akifumi.

In: Biochemical and Biophysical Research Communications, Vol. 456, No. 4, 24.01.2015, p. 860-865.

Research output: Contribution to journalArticle

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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

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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.

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