title: Mature monocytic cells enter tissues and engraft.
abstract: The goal of this study was to identify the circulating cell that is the immediate precursor of tissue macrophages. ROSA 26 marrow mononuclear cells (containing the beta-geo transgene that encodes beta-galactosidase and neomycin resistance activities) were cultured in the presence of macrophage colony-stimulating factor and flt3 Ligand for 6 days to generate monocytic cells at all stages of maturation. Expanded monocyte cells (EMC), the immature (ER-MP12(+)) and more mature (ER-MP20(+)) subpopulations, were transplanted into irradiated B6/129 F2 mice. beta-gal staining of tissue sections from animals 15 min after transplantation demonstrated that the donor cells landed randomly. By 3 h, donor cells in lung and liver were more frequent in animals transplanted with ER-MP20(+) (more mature) EMC than in animals transplanted with unseparated EMC or fresh marrow mononuclear cells, a pattern that persisted at 3 and 7 days. At 3 days, donor cells were found in spleen, liver, lung, and brain (rarely) as clusters as well as individual cells. By 7 and 14 days, the clusters had increased in size, and the cells expressed the macrophage antigen F4/80, suggesting that further replication and differentiation had occurred. PCR for the neogene was used to quantitate the amount of donor DNA in tissues from transplanted animals and confirmed that ER-MP20(+) EMC preferentially engrafted. These data demonstrate that a mature monocytic cell gives rise to tissue macrophages. Because these cells can be expanded and manipulated in vitro, they may be a suitable target population for gene therapy of lysosomal storage diseases.
authors.affiliation: Division of Hematology, Box 357710, University of Washington, Seattle, WA 98195, USA. hemedoc@u.washington.edu
authors.forename: D W
authors.initials: DW
authors.lastname: Kennedy
authors.forename: J L
authors.initials: JL
authors.lastname: Abkowitz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D006085:Graft Survival; D016464:Lysosomal Storage Diseases / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000473:pathology* / Q000637:transplantation*; D051379:Mice; D009000:Monocytes / Q000473:pathology* / Q000637:transplantation*; D014184:Transplantation, Homologous