Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis

Yoon Ok Jang, Sung Hoon Kim, Mee Yon Cho, Kyung Sik Kim, Kyu Sang Park, Seung Kuy Cha, Moon Young Kim, Sei Jin Chang, Soon Koo Baik

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The beneficial effects of simvastatin on fibrosis in various organs have been reported. In addition, bone marrow (BM)-derived mesenchymal stem cells (MSCs) have been suggested as an effective therapy for hepatic fibrosis and cirrhosis. Recent evidence suggests that pharmacological treatment devoted to regulating stem cell function is a potential new therapeutic strategy that is drawing nearer to clinical practice. The aim of this study was to determine whether the combination treatment of simvastatin plus MSCs (Sim-MSCs) could have a synergistic effect on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model and hepatic stellate cells (HSCs). Cirrhotic livers from rats treated with Sim-MSCs exhibited histological improvement compared to those treated with simvastatin alone. Sim-MSCs combination treatment decreased hepatic collagen distribution, lowered the hydroxyproline content, and rescued liver function impairment in rats with TAA-induced cirrhosis. These protective effects were more potent with Sim-MSCs than with simvastatin alone. The upregulation of collagen-1, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, and phospho-Smad3 in cirrhotic livers was prevented by the administration of Sim-MSCs. Intriguingly, Sim-MSCs inhibited both TGF-β/Smad3 signaling and α-SMA in HSCs. The Sim-MSCs combination treatment exerted strong protective effects against hepatic fibrosis by suppressing TGF-β/Smad signaling. Simvastatin could act synergistically with MSCs as an efficient therapeutic approach for intractable cirrhosis.

Original languageEnglish
Pages (from-to)264-271
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume497
Issue number1
DOIs
Publication statusPublished - 2018 Feb 26

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Simvastatin
Stem cells
Mesenchymal Stromal Cells
Bone
Fibrosis
Bone Marrow
Liver
Transforming Growth Factors
Thioacetamide
Rats
Hepatic Stellate Cells
Collagen
Hydroxyproline
Liver Cirrhosis
Smooth Muscle
Muscle
Actins
Up-Regulation
Stem Cells
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis",
abstract = "The beneficial effects of simvastatin on fibrosis in various organs have been reported. In addition, bone marrow (BM)-derived mesenchymal stem cells (MSCs) have been suggested as an effective therapy for hepatic fibrosis and cirrhosis. Recent evidence suggests that pharmacological treatment devoted to regulating stem cell function is a potential new therapeutic strategy that is drawing nearer to clinical practice. The aim of this study was to determine whether the combination treatment of simvastatin plus MSCs (Sim-MSCs) could have a synergistic effect on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model and hepatic stellate cells (HSCs). Cirrhotic livers from rats treated with Sim-MSCs exhibited histological improvement compared to those treated with simvastatin alone. Sim-MSCs combination treatment decreased hepatic collagen distribution, lowered the hydroxyproline content, and rescued liver function impairment in rats with TAA-induced cirrhosis. These protective effects were more potent with Sim-MSCs than with simvastatin alone. The upregulation of collagen-1, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, and phospho-Smad3 in cirrhotic livers was prevented by the administration of Sim-MSCs. Intriguingly, Sim-MSCs inhibited both TGF-β/Smad3 signaling and α-SMA in HSCs. The Sim-MSCs combination treatment exerted strong protective effects against hepatic fibrosis by suppressing TGF-β/Smad signaling. Simvastatin could act synergistically with MSCs as an efficient therapeutic approach for intractable cirrhosis.",
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Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis. / Jang, Yoon Ok; Kim, Sung Hoon; Cho, Mee Yon; Kim, Kyung Sik; Park, Kyu Sang; Cha, Seung Kuy; Kim, Moon Young; Chang, Sei Jin; Baik, Soon Koo.

In: Biochemical and Biophysical Research Communications, Vol. 497, No. 1, 26.02.2018, p. 264-271.

Research output: Contribution to journalArticle

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AU - Jang, Yoon Ok

AU - Kim, Sung Hoon

AU - Cho, Mee Yon

AU - Kim, Kyung Sik

AU - Park, Kyu Sang

AU - Cha, Seung Kuy

AU - Kim, Moon Young

AU - Chang, Sei Jin

AU - Baik, Soon Koo

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