Myelomonocytic cells are sufficient for therapeutic cell fusion in liver

Holger Willenbring, Alexis S. Bailey, Mark Foster, Yassmine Akkari, Craig Dorrell, Susan Olson, Milton Finegold, William H. Fleming, Markus Grompe

Research output: Contribution to journalArticle

339 Scopus citations

Abstract

Liver repopulation with bone marrow-derived hepatocytes (BMHs) can cure the genetic liver disease fumarylacetoacetate hydrolase (Fah) deficiency. BMHs emerge from fusion between donor bone marrow-derived cells and host hepatocytes. To use such in vivo cell fusion efficiently for therapy requires knowing the nature of the hematopoietic cells that fuse with hepatocytes. Here we show that the transplantation into Fah-/- mice of hematopoietic stem cells (HSCs) from lymphocyte-deficient Rag1-/- mice, lineage-committed granulocyte-macrophage progenitors (GMPs) or bone marrow-derived macrophages (BMMs) results in the robust production of BMHs. These results provide direct evidence that committed myelomonocytic cells such as macrophages can produce functional epithelial cells by in vivo fusion. Because stable bone marrow engraftment or HSCs are not required for this process, macrophages or their highly proliferative progenitors provide potential for targeted and well-tolerated cell therapy aimed at organ regeneration.

Original languageEnglish (US)
Pages (from-to)744-748
Number of pages5
JournalNature medicine
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2004

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Willenbring, H., Bailey, A. S., Foster, M., Akkari, Y., Dorrell, C., Olson, S., Finegold, M., Fleming, W. H., & Grompe, M. (2004). Myelomonocytic cells are sufficient for therapeutic cell fusion in liver. Nature medicine, 10(7), 744-748. https://doi.org/10.1038/nm1062