
The endosteal surface of bones is covered not only by a heterogeneous cell population called bone lining cells, , but also by actively bone-producing osteoblasts. Furthermore, the subendosteal region is complex, harboring all cells that line at the interface between the bone surface and the marrow cavity, including stromal cells with differences in their osteogenic and myelopoietic supportive potential. Cells of the sympathetic nerves and osteoclasts were recently described as important components of the niche. In the subendosteal niche, osteoblasts have been proposed to be a crucial component, controlling HSC fate, the size of HSC pool, , and HSC quiescence, by production of factors, such as angiopoietin-1, CXCL12, , and osteopontin. Since the HSC niche was largely defined by their localization in marrow cavity, characterization of the stromal cell population within this niche and their role in the niche are still to be determined. Furthermore, changes in the cellular composition of the niche modify the rate of HSC mobilization and homing. The role of several molecules such as the chemokine CXCL12 (SDF1-α), β1-integrins, and metalloproteinases in homing has been identified -, but the complex interplays of cells and extracellular matrix (ECM) that allow some HSC to lodge at the subendosteal niche while others are actively mobile in the marrow cavity after intravenous injection, are still puzzling. HSC homing to bone marrow is thus a physiological process.

However, HSC can exit the niche, circulate in blood, and eventually return to the BM niche. When they leave it, they enter into the transitional amplifying pool of committed progenitors, followed by terminal differentiation. In this niche, HSC are protected from differentiation and loss of stem cell function possibly by induction of quiescence. In vivo studies have extensively documented the concept of a HSC niche, described as a three-dimensional microenvironment within the subendosteal region of bone marrow (BM) –. Self-renewal and multilineage differentiation capacities that are dependent upon complex cell-autonomous and cell non-autonomous regulatory mechanisms are hallmarks of hematopoietic stem cells (HSC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by grants of the Brazilian agencies Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Pesquisa, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Associação e Programa de Biologia Celular Aplicada a Medicina. Received: JAccepted: JanuPublished: February 8, 2010Ĭopyright: © 2010 de Barros et al. PLoS ONE 5(2):Įditor: Raquel Gonçalves, Universidade do Porto, Portugal

(2010) Osteoblasts and Bone Marrow Mesenchymal Stromal Cells Control Hematopoietic Stem Cell Migration and Proliferation in 3D In Vitro Model. Citation: de Barros APDN, Takiya CM, Garzoni LR, Leal-Ferreira ML, Dutra HS, Chiarini LB, et al.
