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Transplanted Human Cord Blood Cells Give Rise to Hepatocytes in Engrafted Mice

Authors

  • FUMIHIKO ISHIKAWA,

    1. Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
    2. Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
    3. Department of Medicine and Biosystemic Sciences, Kyushu University Graduate School of Medicine, Fukuoka, Japan
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  • CHRISTOPHER J. DRAKE,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, USA
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  • SU YANG,

    1. Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA
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  • PAUL A. FLEMING,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, USA
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  • HITOSHI MINAMIGUCHI,

    1. Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
    2. Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
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  • RICHARD P. VISCONTI,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, USA
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  • CHRISTOPHER V. CROSBY,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, USA
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  • W. SCOTT ARGRAVES,

    1. Department of Cell Biology and Anatomy, Medical University of South Carolina, Charleston, South Carolina, USA
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  • MINE HARADA,

    1. Department of Medicine and Biosystemic Sciences, Kyushu University Graduate School of Medicine, Fukuoka, Japan
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  • L. LYNDON KEY Jr.,

    1. Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA
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  • ANNE G. LIVINGSTON,

    1. Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
    2. Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
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  • JOHN R. WINGARD,

    1. Division of Hematology/Oncology, University of Florida, Gainesville, Florida, USA
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  • MAKIO OGAWA

    Corresponding author
    1. Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
    2. Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
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Address for correspondence: Makio Ogawa, M.D., Ph.D., Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, Charleston, South Carolina 29401-5799. Voice: 843-789-6712; fax: 843-876-5381. ogawam@musc.edu

Abstract

Abstract: Recent studies suggest that rodent hepatocytes may be derived from hematopoietic stem cells. In the current study, the potential hematopoietic origin of hepatocytes was addressed using xenogeneic transplantation of human cord blood cells. CD34+ or CD45+ human cord blood cells were transplanted into “conditioned” newborn NOD/SCID/β2-microglobulinnull mice. At 4 to 5 months post-transplantation, livers of the recipient mice were cryosectioned and examined for evidence of human hepatocyte engraftment using RT-PCR to detect human albumin mRNA, immunohistochemistry to detect human hepatocytic proteins, and fluorescence in situ hybridization (FISH) to detect the presence of human centromeric DNA. Analysis of the bone marrow of transplanted mice revealed that 21.0–45.9% of the cells were human CD45+ cells. FISH analysis of frozen sections of transplanted mouse liver revealed the presence of engrafted cells positive for human centromeric DNA. That engrafted human cells functioned as hepatocytes was indicated by the expression of human albumin mRNA, as judged by RT-PCR. FISH analysis with human and mouse centromeric DNA probes excluded spontaneous cell fusion as the cause for the generation of human hepatocytes. Human cord blood cells can give rise to hepatocytes in a xenogeneic transplantation model. This model will be useful to further characterize the cord blood progenitors of hepatocytes.

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