title: CD146 expression on primary nonhematopoietic bone marrow stem cells is correlated with in situ localization.
abstract: Nonhematopoietic bone marrow mesenchymal stem cells (BM-MSCs) are of central importance for bone marrow stroma and the hematopoietic environment. However, the exact phenotype and anatomical distribution of specified MSC populations in the marrow are unknown. We characterized the phenotype of primary human BM-MSCs and found that all assayable colony-forming units-fibroblast (CFU-Fs) were highly and exclusively enriched not only in the lin⁻/CD271⁺/CD45⁻/CD146⁺ stem-cell fraction, but also in lin⁻/CD271⁺/CD45⁻/CD146(⁻/low) cells. Both populations, regardless of CD146 expression, shared a similar phenotype and genotype, gave rise to typical cultured stromal cells, and formed bone and hematopoietic stroma in vivo. Interestingly, CD146 was up-regulated in normoxia and down-regulated in hypoxia. This was correlated with in situ localization differences, with CD146 coexpressing reticular cells located in perivascular regions, whereas bone-lining MSCs expressed CD271 alone. In both regions, CD34⁺ hematopoietic stem/progenitor cells were located in close proximity to MSCs. These novel findings show that the expression of CD146 differentiates between perivascular versus endosteal localization of non-hematopoietic BM-MSC populations, which may be useful for the study of the hematopoietic environment.
authors.affiliation: Lund Stem Cell Center, University of Lund, Lund, Sweden.
authors.forename: Ariane
authors.initials: A
authors.lastname: Tormin
authors.forename: Ou
authors.initials: O
authors.lastname: Li
authors.forename: Jan Claas
authors.initials: JC
authors.lastname: Brune
authors.forename: Stuart
authors.initials: S
authors.lastname: Walsh
authors.forename: Birgit
authors.initials: B
authors.lastname: Schütz
authors.forename: Mats
authors.initials: M
authors.lastname: Ehinger
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ditzel
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheding
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D051929:CD146 Antigen / Q000096:biosynthesis*; D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D051929:CD146 Antigen