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Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats.
Transplant Proc 2014; 46(4):1198-200TP

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+Show Affiliations

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, 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, 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, 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, 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.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.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, Department of Plastic and Reconstructive 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, 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, 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, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.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, Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24815159

Citation

Chen, K-D, et al. "Regulation of Heme Oxygenase 1 Expression By miR-27b With Stem Cell Therapy for Liver Regeneration in Rats." Transplantation Proceedings, vol. 46, no. 4, 2014, pp. 1198-200.
Chen KD, Hsu LW, Goto S, et al. Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats. Transplant Proc. 2014;46(4):1198-200.
Chen, K. D., Hsu, L. W., Goto, S., Huang, K. T., Nakano, T., Weng, W. T., ... Chen, C. L. (2014). Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats. Transplantation Proceedings, 46(4), pp. 1198-200. doi:10.1016/j.transproceed.2013.12.013.
Chen KD, et al. Regulation of Heme Oxygenase 1 Expression By miR-27b With Stem Cell Therapy for Liver Regeneration in Rats. Transplant Proc. 2014;46(4):1198-200. PubMed PMID: 24815159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats. AU - Chen,K-D, AU - Hsu,L-W, AU - Goto,S, AU - Huang,K-T, AU - Nakano,T, AU - Weng,W-T, AU - Lai,C-Y, AU - Kuo,Y-R, AU - Chiu,K-W, AU - Wang,C-C, AU - Cheng,Y-F, AU - Lin,C-C, AU - Ma,Y-Y, AU - Chen,C-L, PY - 2013/10/01/received PY - 2013/11/26/revised PY - 2013/12/10/accepted PY - 2014/5/13/entrez PY - 2014/5/13/pubmed PY - 2015/1/3/medline SP - 1198 EP - 200 JF - Transplantation proceedings JO - Transplant. Proc. VL - 46 IS - 4 N2 - 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. SN - 1873-2623 UR - https://www.unboundmedicine.com/medline/citation/24815159/Regulation_of_heme_oxygenase_1_expression_by_miR_27b_with_stem_cell_therapy_for_liver_regeneration_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(13)01409-7 DB - PRIME DP - Unbound Medicine ER -