Hematopoietic myelomonocytic cells are the major source of hepatocyte fusion partners.
Several recent reports have demonstrated that transplantation of bone marrow cells can result in the generation of functional hepatocytes. Cellular fusion between bone marrow-derived cells and host hepatocytes has been shown to be the mechanism of this phenomenon. However, the exact identity of the bone marrow cells that mediate cellular fusion has remained undetermined. Here we demonstrate that the hematopoietic progeny of a single hematopoietic stem cell (HSC) is sufficient to produce functional hepatic repopulation. Furthermore, transplantation of lymphocyte-deficient bone marrow cells and in vivo fate mapping of the myeloid lineage revealed that HSC-derived hepatocytes are primarily derived from mature myelomonocytic cells. In addition, using a Cre/lox-based strategy, we directly demonstrate that myeloid cells spontaneously fuse with host hepatocytes. Our findings raise the possibility that differentiated myeloid cells may be useful for future therapeutic applications of in vivo cellular fusion.
Camargo
Fernando D
FD
Center for Cell and Gene Therapy, Baylor College of Medicinem Houston, Texas 77098, USA.
Finegold
Milton
M
Goodell
Margaret A
MA
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002459:Cell Fusion; D019070:Cell Lineage; D002478:Cells, Cultured; D003433:Crosses, Genetic; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology*; D013997:Time Factors
D017493:Leukocyte Common Antigens