Synergistic effects of simvastatin and bone marrow-derived mesenchymal stem cells on hepatic fibrosis
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
- Department of Surgery, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
- Department of Pathology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
- Department of Surgery, Yonsei University College of Medicine, The Liver Cancer Clinic & Pancreatobiliary Cancer Clinic, Severance Hospital, Seoul (Korea, Republic of)
- Department of Physiology, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
- Department of Preventive Medicine and Institute of Occupational Medicine, Yonsei University Wonju College of Medicine, Wonju (Korea, Republic of)
Highlights: • Antifibrotic effect in combination treatment Sim-MSC is superior to simvastatin alone. • Inhibition of TGF-β/Smad signaling is key protective mechanism against hepatic fibrosis in combination Sim-MSC. • The Sim-MSC combination treatment recovered the impaired liver function. 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.
- OSTI ID:
- 23137317
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 497, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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