title: Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment.
abstract: The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident with the establishment of identical subendothelial cells within a miniature bone organ. Establishment of subendothelial stromal cells in developing heterotopic BM in vivo occurs via specific, dynamic interactions with developing sinusoids. Subendothelial stromal cells residing on the sinusoidal wall are major producers of Angiopoietin-1 (a pivotal molecule of the HSC "niche" involved in vascular remodeling). Our data reveal the functional relationships between establishment of the HME in vivo, establishment of skeletal progenitors in BM sinusoids, and angiogenesis.
authors.affiliation: Deparment of Experimental Medicine, La Sapienza University, 00161 Rome, Italy.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Sacchetti
authors.forename: Alessia
authors.initials: A
authors.lastname: Funari
authors.forename: Stefano
authors.initials: S
authors.lastname: Michienzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Cesare
authors.forename: Stefania
authors.initials: S
authors.lastname: Piersanti
authors.forename: Isabella
authors.initials: I
authors.lastname: Saggio
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliafico
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Pamela Gehron
authors.initials: PG
authors.lastname: Robey
authors.forename: Mara
authors.initials: M
authors.lastname: Riminucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianco
mesh_terms: D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000098:blood supply*; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism; D051929:CD146 Antigen / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D051929:CD146 Antigen; C497902:MCAM protein, human