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Cell fusion is the principal source of bone-marrow-derived hepatocytes

Author

Listed:
  • Xin Wang

    (Oregon Health & Science University)

  • Holger Willenbring

    (Oregon Health & Science University)

  • Yassmine Akkari

    (Oregon Health & Science University)

  • Yumi Torimaru

    (Oregon Health & Science University)

  • Mark Foster

    (Oregon Health & Science University)

  • Muhsen Al-Dhalimy

    (Oregon Health & Science University)

  • Eric Lagasse

    (Stem Cells Inc.)

  • Milton Finegold

    (Texas Children's Hospital)

  • Susan Olson

    (Oregon Health & Science University)

  • Markus Grompe

    (Oregon Health & Science University)

Abstract

Evidence suggests that haematopoietic stem cells might have unexpected developmental plasticity, highlighting therapeutic potential. For example, bone-marrow-derived hepatocytes can repopulate the liver of mice with fumarylacetoacetate hydrolase deficiency and correct their liver disease1. To determine the underlying mechanism in this murine model, we performed serial transplantation of bone-marrow-derived hepatocytes. Here we show by Southern blot analysis that the repopulating hepatocytes in the liver were heterozygous for alleles unique to the donor marrow, in contrast to the original homozygous donor cells. Furthermore, cytogenetic analysis of hepatocytes transplanted from female donor mice into male recipients demonstrated 80,XXXY (diploid to diploid fusion) and 120,XXXXYY (diploid to tetraploid fusion) karyotypes, indicative of fusion between donor and host cells. We conclude that hepatocytes derived form bone marrow arise from cell fusion and not by differentiation of haematopoietic stem cells.

Suggested Citation

  • Xin Wang & Holger Willenbring & Yassmine Akkari & Yumi Torimaru & Mark Foster & Muhsen Al-Dhalimy & Eric Lagasse & Milton Finegold & Susan Olson & Markus Grompe, 2003. "Cell fusion is the principal source of bone-marrow-derived hepatocytes," Nature, Nature, vol. 422(6934), pages 897-901, April.
    • Handle: RePEc:nat:nature:v:422:y:2003:i:6934:d:10.1038_nature01531
    DOI: 10.1038/nature01531
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    Cited by:

    1. Hussein Abdellatif, 2018. "Oval Cells - Potential Role in Liver Regeneration," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 2(1), pages 2227-2234, January.

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