Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (29): 4656-4661.doi: 10.3969/j.issn.2095-4344.1794

Previous Articles     Next Articles

Long-chain non-coding RNA highly up-regulated in liver cancer promotes the differentiation of human bone marrow mesenchymal stem cells into hepatocytes 

Li Meng1, Zhou Yun2, Yu Yabin3, Wang Chaoqun1, Gong Yusen1   

  1. 1Department of Pathology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China; 2Department of Radiation Oncology, Xuzhou Central Hospital, Xuzhou 221004, Jiangsu Province, China; 3Department of Hepatobiliary and Pancreatic Surgery, Huaian First People’s Hospital, Huaian 223300, Jiangsu Province, China
  • Revised:2019-04-07 Online:2019-10-18 Published:2019-10-18
  • Contact: Gong Yusen, Master, Chief physician, Department of Pathology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
  • About author:Li Meng, Master candidate, Department of Pathology, Xuzhou Medical University, Xuzhou 221004, Jiangsu Province, China
  • Supported by:

    the Science and Technology Research Project of Xuzhou City, No. KC17111 (to ZY)

Abstract:

BACKGROUND: Human bone marrow mesenchymal stem cells can be induced to differentiate into hapatocytes without mature function. Long-chain non-coding RNA (lncRNA) plays an important part in the differentiation of mesenchymal stem cells. To date, there is still no report on whether the lncRNA highly up-regulated in liver cancer (HULC) is involved in the differentiation of bone marrow mesenchymal stem cells into hepatocytes.
OBJECTIVE: To investigate the mechanism of lncRNA HULC in the differentiation of human bone marrow mesenchymal stem cells into hepatocyte-like cells.
METHODS: Human bone marrow mesenchymal stem cells were purchased from the Cell Bank of Chinese Academy of Sciences, Shanghai, China and were cultured in the hepatic differentiation medium containing cytokines in vitro. After 4 weeks of induction, cell morphology was observed under inverted microscope. Hepatocyte specific proteins were analyzed by immunofluorescence. The expression of IncRNA HULC was examined by qRT-PCR. Bone marrow mesenchymal cell lines stably expressing IncRNA HULC were then produced through lentiviral transfection. Bone marrow mesenchymal stem cells transfected with negative lentivirus were used as controls. Two groups of cells were concurrently induced with the hepatic differentiation medium containing cytokines. The expressions of hepatocyte specific genes and proteins were detected and compared between the two groups by qRT-PCR and western blot, respectively.
RESULTS AND CONCLUSION: Human bone marrow mesenchymal stem cells could be successfully induced into hepatocytes in vitro through the addition of cytokines. The expression of IncRNA HULC was gradually increased during the differentiation. Overexpression of IncRNA HULC caused a marked increase in the expression of hepatocyte specific genes and proteins. To conclude, IncRNA HULC plays an important role in the differentiation of human bone marrow mesenchymal stem cells into hepatocytes. It will provide a theoretical basis for the application of cell therapy in liver diseases.

Key words: long-chain non-coding RNA, highly up-regulated in liver cancer, bone marrow mesenchymal stem cells, hepatocytes, cell differentiation, hepatocyte specific genes

CLC Number: