title: Direct induction of hepatocyte-like cells from immortalized human bone marrow mesenchymal stem cells by overexpression of HNF4α.
abstract: Hepatocytes from human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are expected to be a useful source for cell transplantation. However, relatively low efficiency and repeatability of hepatic differentiation of human BM-MSCs remains an obstacle for clinical translation. Hepatocyte nuclear factor 4 alpha (HNF4α), a critical transcription factor, plays an essential role in the entire process of liver development. In this study, immortalized hBM-MSCs, UE7T-13 cells were transduced with a lentiviral vector containing HNF4α. The typical fibroblast-like morphology of the MSCs changed, and polygonal, epithelioid cells grew out after HNF4α transduction. In hepatocyte culture medium, HNF4α-transduced MSCs (E7-hHNF4α cells) strongly expressed the albumin (ALB), CYP2B6, alpha-1 antitrypsin (AAT), and FOXA2 mRNA and exhibited morphology markedly similar to that of mature hepatocytes. The E7-hHNF4α cells showed hepatic functions such as Indocyanine green (ICG) uptake and release, glycogen storage, urea production and ALB secretion. Approximately 28% of E7-hHNF4α cells expressed both ALB and AAT. Furthermore, these E7-hHNF4α cells via superior mesenteric vein (SMV) injection expressed human ALB in mouse chronic injured liver. In conclusion, this study represents a novel strategy by directly inducing hepatocyte-like cells from MSCs.
authors: Interventional Medicine Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China; The department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China; Guang Dong Provincial Engineering Research Center of Molecular Imaging, Zhuhai, China.
authors: Xiaojun
authors: X
authors: Hu
authors: Department of Radiology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Peiyi
authors: P
authors: Xie
authors: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors: Weiqiang
authors: W
authors: Li
authors: The department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors: Zhengran
authors: Z
authors: Li
authors: Interventional Medicine Center, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China; Interventional Radiology Institute, Sun Yat-sen University, Zhuhai, China; Guang Dong Provincial Engineering Research Center of Molecular Imaging, Zhuhai, China. Electronic address: shanhong@mail.sysu.edu.cn.
authors: Hong
authors: H
authors: Shan
mesh_terms: D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta / Q000235:genetics / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation*; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014161:Transduction, Genetic; D014508:Urea / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
chemical_list: D000418:Albumins; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C496502:FOXA2 protein, human; C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; C411023:anti-Fas monoclonal antibody; D051542:Hepatocyte Nuclear Factor 3-beta; D014508:Urea; D006003:Glycogen; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6
keywords: Hepatocyte nuclear factor 4 alpha; Hepatocyte-like cells; Mesenchymal stem cells