Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells

被引:307
|
作者
Kortesidis, A
Zannettino, A
Isenmann, S
Shi, ST
Lapidot, T
Gronthos, S
机构
[1] Hanson Inst, Inst Med & Vet Sci, Mesenchymal Stem Cell Grp, Div Hematol, Adelaide, SA 5000, Australia
[2] Hanson Inst, Inst Med & Vet Sci, Div Haematol, Myeloma & Mesenchymal Res Grp,Matthew Roberts Fdn, Adelaide, SA, Australia
[3] NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA
[4] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
关键词
D O I
10.1182/blood-2004-11-4349
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 interieukin-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. (c) 2005 by The American Society of Hematology.
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收藏
页码:3793 / 3801
页数:9
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