Permanent engraftment and function of hepatocytes delivered to the liver: Implications for gene therapy and Liver Repopulation

Authors

  • Sanjeev Gupta M.D.,

    Corresponding author
    1. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461
    2. Department of Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    • Ullman 625, Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461
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  • Emma Aragona,

    1. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461
    2. Department of Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
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  • Ravikumar P. Vemuru,

    1. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461
    2. Department of Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
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  • Kuldeep K. Bhargava,

    1. Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, New York 10461
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  • Robert D. Burk,

    1. Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461
    2. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461
    3. Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York 10461
    4. Department of Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
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  • Jayanta Roy Chowdhury

    1. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461
    2. Department of Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
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Abstract

To examine the distribution of intrasplenically transplanted hepatocytes, we used HBsAg-producing G7 HBV transgenic hepatocytes or cells labeled with 111In. Most hepatocytes translocated to the liver (55% ± 7%; mean ± S.D.); the spleen retained a smaller fraction (15% ± 3%); and some transplanted cells localized in lungs (3%) or pancreas (1%). Transplanted hepatocytes were rapidly assimilated into the liver lobule. Morphometrical quantitation indicated that the numbers of transplanted hepatocytes in the liver at 48 hr and at 9 mo after transplantation were similar. Serum HBsAg was detected in recipients of the G7 HBV hepatocytes during the 1-yr experiment. These results indicate that a large number of hepatocytes can be reproducibly delivered to the liver by transplantation into the spleen. Transplanted hepatocytes engraft rapidly, assimilate into host liver, maintain normal function and survive permanently. Systems for safe delivery and localization of hepatocytes in the liver represent a critical step toward successfully accomplishing hepatocyte-directed gene therapy and repopulation of the acutely devastated liver. (HEPATOLOGY 1991;14:144–149.)

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