Differentiation of human umbilical cord mesenchymal stem cells into hepatocyte-like cells by hTERT gene transfection in vitro

Authors

  • Xu-Jing Liang,

    Corresponding author
    1. Department of Infectious Disease, The First Affiliated Hospital, Jinan University, 510630 Guangzhou, Guangdong, Peoples Republic of China
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  • Xiao-Jia Chen,

    Corresponding author
    1. Bioengineering Institute, Jinan University, 510630 Guangzhou, Guangdong, Peoples Republic of China
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  • Dong-Hua Yang,

    1. Department of Gastroenterology, The First Affiliated Hospital, Jinan University, 510630 Guangzhou, Guangdong, Peoples Republic of China
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  • Si-Min Huang,

    1. Department of Infectious Disease, The First Affiliated Hospital, Jinan University, 510630 Guangzhou, Guangdong, Peoples Republic of China
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  • Guo-Dong Sun,

    1. Department of Orthopaedic Surgery, The First Affiliated Hospital, Jinan University, 510630 Guangzhou, Guangdong, Peoples Republic of China
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  • You-Peng Chen

    Corresponding author
    1. Department of Infectious Disease, The First Affiliated Hospital, Jinan University, 510630 Guangzhou, Guangdong, Peoples Republic of China
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These authors have contributed equally to this work.

To whom correspondence should be addressed (email typchen@jnu.edu.cn).

Abstract

The availability of a large quantity of MSCs (mesenchymal stem cells) would greatly advance liver-directed cell therapies. However, MSCs have a limited lifespan in vitro. Therefore we tested whether hUCMSCs (human umbilical cord MSCs) could be immortalized by transduction with a lentiviral vector carrying the hTERT (human telomerase reverse transcriptase) catalytic subunit gene, and investigated their differentiation potential. Transfected hUCMSCs overexpressed the hTERT gene and up-regulated their telomerase activity. The transfected hUCMSCs maintained their typical morphology and MSC-specific markers, and vigorously proliferated, undergoing more than 100 PDs (population doublings) to date. Following incubation with hepatogenic agents, the transfected hUCMSCs differentiated into hepatocyte-like cells, and expressed hepatic markers, such as albumin, AFP (α-fetoprotein) and CK-18 (cytokeratin-18). Transfected hUCMSCs showed no transformation into tumours in nude mice. In conclusion, telomerization of hUCMSCs by hTERT overexpression extends their replicative lifespan without influencing their hepatogenic differentiation potential. This offers opportunities for obtaining sufficient quantities of cells for liver-directed therapies.

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