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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3793-3801.
Prepublished online as a Blood First Edition Paper on January 27, 2005; DOI 10.1182/blood-2004-11-4349.
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CHEMOKINES
Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells
Angela Kortesidis,
Andrew Zannettino,
Sandra Isenmann,
Songtao Shi,
Tsvee Lapidot, and
Stan Gronthos
From the Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science/Hanson Institute, Adelaide, South Australia, Australia; Myeloma and Mesenchymal Research Group, Matthew Roberts Foundation Laboratory, Division of Haematology, Institute of Medical and Veterinary Science/Hanson Institute, Adelaide, South Australia, Australia; Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD; and Department of Immunology, The Wiezmann Institute of Science, Rehovot, Israel.
The maintenance of bone marrow stromal stem cells (BMSSCs) is tightly controlled by the local microenvironment and by autocrine regulatory factors secreted by BMSSCs. To identify such factors, a cDNA subtraction library was generated from purified BMSSCs, based on their high expression of the STRO-1 antigen. Stromal-derived factor-1 (SDF-1) was one differentially expressed gene highly expressed by purified BMSSCs prior to culture. In vitro, immature preosteogenic cells expressed greater levels of SDF-1 when compared with mature cell types representative of osteoblasts and osteocytes/bone lining cells. Furthermore, SDF-1 expression was rapidly down-regulated when BMSSCs were cultured under osteoinductive conditions. BMSSCs were also shown to express functional cell surface SDF-1 receptors (CXCR4). Transduced BMSSC lines, secreting high SDF-1 levels, displayed an enhanced ability to form ectopic bone in vivo, in comparison with control BMSSC lines. Moreover, high SDF-1–expressing BMSSCs displayed an increased capacity for cellular growth and protection against interleukin-4–induced apoptosis. Similarly, fibroblast colony-forming units (CFU-Fs) also displayed increased growth and resistance to  -interferon-2a–induced apoptosis, in synergy with platelet-derived growth factor BB (PDGF-BB) and SDF-1 in vitro. These studies indicate that the chemokine, SDF-1, may play a role in the maintenance, survival, and osteogenic capacity of immature BMSSC populations.
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