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Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells

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Abstract

Orthotopic liver transplantation (OLT) is the only proven effective treatment for both end-stage and metabolic liver diseases. Hepatocyte transplantation is a promising alternative for OLT, but the lack of available donor livers has hampered its clinical application. Hepatocyte-like cells (HLCs) differentiated from many multi-potential stem cells can help repair damaged liver tissue. Yet almost suitable cells currently identified for human use are difficult to harvest and involve invasive procedures. Recently, a novel mesenchymal stem cell derived from human menstrual blood (MenSC) has been discovered and obtained easily and repeatedly. In this study, we examined whether the MenSCs are able to differentiate into functional HLCs in vitro. After three weeks of incubation in hepatogenic differentiation medium containing hepatocyte growth factor (HGF), fibroblast growth factor-4 (FGF-4), and oncostain M (OSM), cuboidal HLCs were observed, and cells also expressed hepatocyte-specific marker genes including albumin (ALB), α-fetoprotein (AFP), cytokeratin 18/19 (CK18/19), and cytochrome P450 1A1/3A4 (CYP1A1/3A4). Differentiated cells further demonstrated in vitro mature hepatocyte functions such as urea synthesis, glycogen storage, and indocyanine green (ICG) uptake. After intrasplenic transplantation into mice with 2/3 partial hepatectomy, the MenSC-derived HLCs were detected in recipient livers and expressed human ALB protein. We also showed that MenSC-derived HLC transplantation could restore the serum ALB level and significantly suppressed transaminase activity of liver injury animals. In conclusion, MenSCs may serve as an ideal, easily accessible source of material for tissue engineering and cell therapy of liver tissues.

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Authors and Affiliations

  1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China

    Xiao-zhou Mou, Jian Lin, Yi-fei Li, Xiao-xing Wu, Bing-yu Xiang & Charlie Xiang

  2. Institute for Cell-Based Drug Development of Zhejiang Province, Hangzhou, 310058, China

    Xiao-zhou Mou, Jin-yang Chen & Charlie Xiang

  3. People’s Hospital of Tongling, Tongling, 244000, China

    Jian Lin

  4. S-Evans Biosciences, Hangzhou, 311121, China

    Jin-yang Chen

  5. The 117th Hospital of PLA, Hangzhou, 310013, China

    Cai-yun Li & Ju-ming Ma

  6. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, 310003, China

    Charlie Xiang

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  1. Xiao-zhou Mou
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  2. Jian Lin
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  3. Jin-yang Chen
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  4. Yi-fei Li
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  9. Charlie Xiang
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Correspondence to Ju-ming Ma or Charlie Xiang.

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The two authors contributed equally to this work

Project supported by the National High-Tech R&D Program (863) of China (Nos. 2011AA020102 and 2012AA020905), the Key Technologies R&D Program of Zhejiang Province (Nos. 2012C13015-2 and 2011C13029-1), the Hangzhou Key Technologies R&D Program (No. 20122513A49), and the National Natural Science Foundation of China (Nos. 81201783 and 81201089)

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Mou, Xz., Lin, J., Chen, Jy. et al. Menstrual blood-derived mesenchymal stem cells differentiate into functional hepatocyte-like cells. J. Zhejiang Univ. Sci. B 14, 961–972 (2013). https://doi.org/10.1631/jzus.B1300081

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