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Reversibly immortalized hepatic progenitor cell line containing double suicide genes

  • Authors:
    • Shu‑Yu Fang
    • Chao‑Qun Hu
    • Meng‑Nan Liu
    • Li Tao
    • Yi Wang
    • Meng‑Jia Gong
    • Yun He
    • Tong‑Chuan He
    • Yang Bi
  • View Affiliations / Copyright

    Affiliations: Department of Pediatric Surgery, Stem Cell Biology and Therapy Laboratory, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Stem Cell Therapy Engineering Technical Center, The Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China
    Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1977-1986
    |
    Published online on: August 2, 2018
       https://doi.org/10.3892/ijmm.2018.3803
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Abstract

A large number of functional hepatocytes is required for bioartificial liver therapy. Simian virus 40 T‑antigen (SV40T) has been previously reported to improve the immortalized proliferation of primary hepatocytes to generate a sufficient number of cells; however, these long‑term immortalized hepatocytes may induce further malignant transformation in vivo. In the present study, the SV40T immortalization gene and two suicide genes, herpes simplex virus thymidine kinase (HSV‑tk) and cytosine deaminase (CD), were transducted into primary hepatocytes to construct a novel type of Cre/LoxP‑mediated reversible immortalized hepatocyte line. Polymerase chain reaction analysis and western blotting confirmed that the SV40T, HSV‑tk and CD genes were successfully inserted into hepatic progenitor cells and their expression was controlled by Cre/LoxP recombination. Total removal of SV40T could be achieved via the ganciclovir (GCV)/HSV‑tk suicide system. Cells maintained their biosafety in vivo with CD gene expression and 5‑fluorocytosine (5‑FC) induced cell death. Following transplantation into the carbon tetrachloride (CCl4) model group, the majority of cells had survived after 14 days post‑implantation and a number of the cells had transported into the liver parenchyma. When compared with the CCl4 model group, the transplanted cells repaired the liver biochemical index and pathological structure markedly. Thus, the present study reports a novel reversible immortalized hepatocyte with double suicide genes, which exhibited the cellular phenotype and recovery function of normal liver cells. This method maximally guaranteed the biological safety of immortalized hepatocytes for in vivo application, providing a reliable, safe and ideal cell material for the artificial liver technique.
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Copy and paste a formatted citation
Spandidos Publications style
Fang SY, Hu CQ, Liu MN, Tao L, Wang Y, Gong MJ, He Y, He TC and Bi Y: Reversibly immortalized hepatic progenitor cell line containing double suicide genes. Int J Mol Med 42: 1977-1986, 2018.
APA
Fang, S., Hu, C., Liu, M., Tao, L., Wang, Y., Gong, M. ... Bi, Y. (2018). Reversibly immortalized hepatic progenitor cell line containing double suicide genes. International Journal of Molecular Medicine, 42, 1977-1986. https://doi.org/10.3892/ijmm.2018.3803
MLA
Fang, S., Hu, C., Liu, M., Tao, L., Wang, Y., Gong, M., He, Y., He, T., Bi, Y."Reversibly immortalized hepatic progenitor cell line containing double suicide genes". International Journal of Molecular Medicine 42.4 (2018): 1977-1986.
Chicago
Fang, S., Hu, C., Liu, M., Tao, L., Wang, Y., Gong, M., He, Y., He, T., Bi, Y."Reversibly immortalized hepatic progenitor cell line containing double suicide genes". International Journal of Molecular Medicine 42, no. 4 (2018): 1977-1986. https://doi.org/10.3892/ijmm.2018.3803
Copy and paste a formatted citation
x
Spandidos Publications style
Fang SY, Hu CQ, Liu MN, Tao L, Wang Y, Gong MJ, He Y, He TC and Bi Y: Reversibly immortalized hepatic progenitor cell line containing double suicide genes. Int J Mol Med 42: 1977-1986, 2018.
APA
Fang, S., Hu, C., Liu, M., Tao, L., Wang, Y., Gong, M. ... Bi, Y. (2018). Reversibly immortalized hepatic progenitor cell line containing double suicide genes. International Journal of Molecular Medicine, 42, 1977-1986. https://doi.org/10.3892/ijmm.2018.3803
MLA
Fang, S., Hu, C., Liu, M., Tao, L., Wang, Y., Gong, M., He, Y., He, T., Bi, Y."Reversibly immortalized hepatic progenitor cell line containing double suicide genes". International Journal of Molecular Medicine 42.4 (2018): 1977-1986.
Chicago
Fang, S., Hu, C., Liu, M., Tao, L., Wang, Y., Gong, M., He, Y., He, T., Bi, Y."Reversibly immortalized hepatic progenitor cell line containing double suicide genes". International Journal of Molecular Medicine 42, no. 4 (2018): 1977-1986. https://doi.org/10.3892/ijmm.2018.3803
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