Myelomonocytic cells are sufficient for therapeutic cell fusion in liver.
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.
Willenbring
Holger
H
Department of Molecular and Medical Genetics, Oregon Stem Cell Center, Oregon Health & Science University, Portland, Oregon 97239, USA. willenbr@ohsu.edu
Bailey
Alexis S
AS
Foster
Mark
M
Akkari
Yassmine
Y
Dorrell
Craig
C
Olson
Susan
S
Finegold
Milton
M
Fleming
William H
WH
Grompe
Markus
M
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
D006867:Hydrolases; C020156:fumarylacetoacetase