Human progenitor cells with high aldehyde dehydrogenase activity efficiently engraft into damaged liver in a novel model

Authors

  • Ping Zhou,

    1. Stem Cell Program, University of California Davis Medical Center, Sacramento, CA
    2. Division of Oncology, Washington University School of Medicine, St. Louis, MO
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  • Sara Hohm,

    1. Division of Oncology, Washington University School of Medicine, St. Louis, MO
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  • Yetunde Olusanya,

    1. Stem Cell Program, University of California Davis Medical Center, Sacramento, CA
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  • David A. Hess,

    1. Division of Oncology, Washington University School of Medicine, St. Louis, MO
    2. Krembil Center for Stem Cell Biology, Robarts Research Institute, London, Ontario, Canada
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  • Jan Nolta

    Corresponding author
    1. Stem Cell Program, University of California Davis Medical Center, Sacramento, CA
    2. Division of Oncology, Washington University School of Medicine, St. Louis, MO
    • Stem Cell Program, Department of Internal Medicine, University of California Davis, 2700 Stockton Boulevard, Room 2132, Sacramento, CA 95817
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    • fax: 916-703-9310.


  • Potential conflict of interest: Nothing to report.

Abstract

Human cord blood stem cells (hCBSCs) have been reported to generate hepatocyte-like cells and thus hold promise for repairing damaged liver. However, the frequency of hCBSC-derived hepatocytes varies tremendously between different studies, and it is still controversial as to whether hCBSC-derived cells can transdifferentiate into hepatocytes or simply fuse to recipient hepatocytes. We used the β-glucuronidase–deficient nonobese diabetic/severe combined immunodeficient/mucopolysaccharidosis type VII (NOD/SCID/MPSVII) mouse model for better identification of engrafted cells. We transplanted lineage-depleted human umbilical cord blood–derived cells with high aldehyde dehydrogenase activity (ALDHhiLin) into irradiated NOD/SCID/MPSVII mice followed by carbon tetrachloride administration to induced liver damage. ALDHhiLin cells were efficiently engrafted in the recipient mouse livers and improved recovery of the mice from toxic insult. The percentage of human cells in these livers ranged between 3% and 14.2% using quantitative real-time polymerase chain reaction. Furthermore, human-originated cells expressing liver-specific α1-antitrypsin messenger RNA, albumin and hepatocyte nuclear factor 1 protein were detected in the recipient livers. Interestingly, human versus murine centromeric fluorescent in situ hybridization analysis on the liver sections demonstrated that most human cells were not fused to mouse cells. However, the majority of the human originated albumin-expressing cells also carried mouse genetic material, hence were the product of cell fusion. Conclusion: hCBSCs or their progeny may home to the injured liver and release trophic factors that hasten tissue repair, whereas fusion of these cells with hepatocytes may occur rarely and contribute to a lesser extent to liver repair. (HEPATOLOGY 2009.)

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