Overexpression of hepatocyte nuclear factor 4α in umbilical cord mesenchymal stem cells promotes liver regeneration after subtotal hepatectomy in mice
  
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DOI:10.11915/j.issn.1671-5403.2015.01.016
Key words:mice  liver regeneration  mesenchymal stem cells  hepatocyte nuclear factor 4α
Author NameAffiliationE-mail
WU Ning1, MA Yong1, ZHAI Xiu-Yu2, ZHANG Yu-Ling3, ZHANG Yong1, ZHANG Qi-Qi4, HANG Hua-Lian4, XIA Qiang4, BIAN Jian-Min1* 1Department of General Surgery, Nanjing Hospital Affiliated to Nanjing Medical University, Nanjing 210006, China
2the Second Department of Urology, the First Hospital of Jilin University, Jilin 130021, China
3Guizhou Provincial Key Laboratory of Cell Engineering, Affiliated Hospital of Zunyi Medical College, Zunyi 563033, China
4Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China 
jmbian0324@gmail.com 
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Abstract:
      Objective To investigate whether human umbilical cord mesenchymal stem cells (UC-MSC) and the cells with overexpression of hepatocyte nuclear factor 4α (HNF4α) can promote liver regeneration after subtotal hepatectomy in mice. Methods After human UC-MSC were isolated, cultured and identified, the cells were transfected with lentiviral vector LV-HNF4α. Then the cell supernatant was collected and cultured with L02 cells, and the L02 cell viability was detected by cell counting kit-8 (CCK8) assay. In the in vivo study, a total of 18 mice were randomly divided into 3 groups (n=6 for each group): normal saline (NS) group, MSC group and MSC-HNF4α group, and received an injection of NS, MSC and MSC-HNF4α (5×106/ml), respectively via tail vein in 2 h before the establishment of subtotal hepatectomy model (70%). In 48 h later, the expression of Ki67 in the liver tissues was detected by immunohistochemical assay, and the results were compared among 3 groups. Results UC-MSC was successfully isolated from human umbilical cord, and the UC-MSC with stable overexpression of HNF4α were established. In vitro study indicated that the L02 cells showed stronger proliferative ability when cocultured with MSC and MSC-HNF4α than cultured alone (P<0.01), and those cocultured with MSC-HNF4α stronger than the cells with MSC (P<0.05). In vivo study showed similar findings: the expression of Ki67 was stronger in the mice treated with MSC or MSC-HNF4α than those with NS (P<0.01), and also overexpression of HNF4α resulted in more significant expression of Ki67 (P<0.05). Conclusion Both MSC and MSC-HNF4α secret some cytokines to promote liver regeneration.
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