title: Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats.
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.
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: K-D
authors.initials: KD
authors.lastname: Chen
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: L-W
authors.initials: LW
authors.lastname: Hsu
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: S
authors.initials: S
authors.lastname: Goto
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: K-T
authors.initials: KT
authors.lastname: Huang
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Graduate Institute of Clinical Medical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: T
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: W-T
authors.initials: WT
authors.lastname: Weng
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lai
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Plastic and Reconstructive Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Y-R
authors.initials: YR
authors.lastname: Kuo
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: K-W
authors.initials: KW
authors.lastname: Chiu
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Cheng
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: clchen@adm.cgmh.org.tw.
authors.forename: C-L
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006498:Hepatectomy; D006505:Hepatitis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D034622:RNA Interference; D011917:Rats, Inbred Lew; D013997:Time Factors; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; C000594049:MIRN27 microRNA, rat; D035683:MicroRNAs; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat