Regulation of Heme Oxygenase 1 Expression by miR-27b With Stem Cell Therapy for Liver Regeneration in Rats

• Published in: Transplantation proceedings 2014-05, Vol.46 (4), p.1198-1200
• Main Authors: Chen, K.-D, Hsu, L.-W, Goto, S, Huang, K.-T, Nakano, T, Weng, W.-T, Lai, C.-Y, Kuo, Y.-R, Chiu, K.-W, Wang, C.-C, Cheng, Y.-F, Lin, C.-C, Ma, Y.-Y, Chen, C.-L
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Adipose Tissue - immunology; Adipose Tissue - metabolism; Adipose Tissue - transplantation; Animals; Cell Proliferation - drug effects; Cells, Cultured; Enzyme Inhibitors - pharmacology; Female; Gene Expression Regulation, Enzymologic; Heme Oxygenase (Decyclizing) - antagonists & inhibitors; Heme Oxygenase (Decyclizing) - genetics; Heme Oxygenase (Decyclizing) - metabolism; Hepatectomy; Hepatitis - enzymology; Hepatitis - pathology; Hepatitis - prevention & control; Liver - drug effects; Liver - enzymology; Liver - immunology; Liver - pathology; Liver Cirrhosis - enzymology; Liver Cirrhosis - pathology; Liver Cirrhosis - prevention & control; Liver Regeneration - drug effects; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - immunology; Mesenchymal Stromal Cells - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Animal; Rats, Inbred Lew; RNA Interference; Surgery; Time Factors; Transfection
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2013.12.013

Abstract Adipose-derived mesenchymal stem cells (ASCs) have been considered to be attractive and readily available adult mesenchymal stem cells (MSCs) and are becoming increasingly popular for use in regenerating cell therapy. However, recent evidence attributed a fibrotic potential to MSCs which differentiated into myofibroblasts with highly increased α-smooth muscle actin (α-SMA) expression while transplanted into an injured/regenerating liver in mice. In this study, we studied the role of miR-27b in ASCs and their regenerative potential after partial liver resection in rats. ASCs transfected with control siRNA or miR-27b were intravenously injected into autologous rats undergoing 70% partial hepatectomy (PH). Our data showed that the regenerative capacities of ASCs with overexpressed miR-27b were significantly higher compared with control ASCs. However, the enhanced regeneration, hepatic differentiation, and suppressed liver inflammation, as well as fibrotic activity, were significantly reverted by ZnPP coadministration (heme oxygenase-1 [HO-1] inhibitor) indicating an important role of HO-1 in the regenerating and cytoprotective activities of miR-27b–transfected ASCs. We demonstrated that administration of autologous ASCs overexpressed with miR-27b enhances rapid and early liver regeneration and, importantly, preserves function after PH. The ASCs with miR-27b overexpression might offer a viable therapeutic option to facilitate rapid recovery after liver resection.