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

Xin Wang, Holger Willenbring, Yassmine Akkari, Yumi Torimaru, Mark Foster, Muhsen Al-Dhalimy, Eric Lagasse, Milton Finegold, Susan Olson and Markus Grompe ()
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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

Nature, 2003, vol. 422, issue 6934, 897-901

Abstract: 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.

Date: 2003
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DOI: 10.1038/nature01531

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