title: Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells.
abstract: 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 alpha-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.
authors.affiliation: Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science/Hanson Institute, Frome Rd, Adelaide 5000, South Australia, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Kortesidis
authors.forename: Andrew
authors.initials: A
authors.lastname: Zannettino
authors.forename: Sandra
authors.initials: S
authors.lastname: Isenmann
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
authors.forename: Stan
authors.initials: S
authors.lastname: Gronthos
mesh_terms: D000328:Adult; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010012:Osteogenesis; D019718:Receptors, CXCR4 / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4