title: Myelomonocytic cells are sufficient for therapeutic cell fusion in liver.
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.
authors.affiliation: Department of Molecular and Medical Genetics, Oregon Stem Cell Center, Oregon Health & Science University, Portland, Oregon 97239, USA. willenbr@ohsu.edu
authors.forename: Holger
authors.initials: H
authors.lastname: Willenbring
authors.forename: Alexis S
authors.initials: AS
authors.lastname: Bailey
authors.forename: Mark
authors.initials: M
authors.lastname: Foster
authors.forename: Yassmine
authors.initials: Y
authors.lastname: Akkari
authors.forename: Craig
authors.initials: C
authors.lastname: Dorrell
authors.forename: Susan
authors.initials: S
authors.lastname: Olson
authors.forename: Milton
authors.initials: M
authors.lastname: Finegold
authors.forename: William H
authors.initials: WH
authors.lastname: Fleming
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
mesh_terms: D000818:Animals; D002459:Cell Fusion; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D022781:Hepatocytes / Q000166:cytology*; D006867:Hydrolases / Q000172:deficiency*; D008115:Liver Regeneration; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D006867:Hydrolases; C020156:fumarylacetoacetase