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Bone marrow subendosteal microenvironment harbours functionally distinct haemosupportive stromal cell populations

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Abstract

In adult animals, bone marrow is the major site of blood cell production, which is controlled by interactions between the local stroma and blood cell progenitors. The endosteal/subendosteal environment comprises bone-lining and adjacent reticular cells and sustains haemopoietic stem cell (HSC) self-renewal, proliferation and differentiation. We have questioned the specific role of each of these stroma cells in controlling HSC fate. We have isolated two distinct stroma-cell populations containing subendosteal reticulocytes (F-RET) and osteoblasts (F-OST) from periosteum-free fragments of murine femurs by a two-step collagenase-digestion procedure. Both populations produce similar extracellular matrix (collagen I, laminin, fibronectin, decorin), except for collagen IV, which is low in F-OST. They also express osteogenic markers: osteopontin, osteonectin, bone sialoprotein and alkaline phosphatase (ALP). The quantity and activity of ALP are however higher in F-OST. When co-cultured with bone marrow mononuclear cells or lineage-negative haemopoietic progenitors, F-OST stroma induces low proliferation and high maintenance of early haemopoietic progenitors, whereas F-RET stroma induces high short-term proliferation and differentiation. Analysis by reverse transcription/polymerase chain reaction has revealed higher levels of Jagged-1 expression by F-OST cells than by the F-RET population. Thus, two adjacent stroma cells (subendosteal and endosteal) play distinct roles in controlling the stem-cell capacity and fate of HSC and probably contribute distinctly to HSC niche formation.

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Acknowledgements

We thank Marcia Soares Sader for her kind support with the scanning electron microscopy and Dr. Maria Isabel Doria Rossi for her expertise and contributions during this work.

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Authors and Affiliations

  1. Departamento de Histologia e Embriologia, Instituto de Ciências Biomédicas, Cidade Universitária, 21941-970, Rio de Janeiro, Brasil

    Alex Balduino, Sandra P. Hurtado, Priscilla Frazão, Christina M. Takiya, Leandro M. Alves, Luiz-Eurico Nasciutti, Márcia C. El-Cheikh & Radovan Borojevic

  2. Programa Avançado de Biologia Celular Aplicada à Medicina, Hospital Universitário Clementino Fraga Filho, Cidade Universitária, Caixa Postal 68021, 21941-970, Rio de Janeiro, Brasil

    Radovan Borojevic

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  1. Alex Balduino
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  2. Sandra P. Hurtado
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Correspondence to Radovan Borojevic.

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Balduino, A., Hurtado, S.P., Frazão, P. et al. Bone marrow subendosteal microenvironment harbours functionally distinct haemosupportive stromal cell populations. Cell Tissue Res 319, 255–266 (2005). https://doi.org/10.1007/s00441-004-1006-3

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