THE STRO-1(+) FRACTION OF ADULT HUMAN BONE-MARROW CONTAINS THE OSTEOGENIC PRECURSORS
THE STRO-1(+) FRACTION OF ADULT HUMAN BONE-MARROW CONTAINS THE OSTEOGENIC PRECURSORS
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DOI：
10.1182/blood.v84.12.4164.bloodjournal84124164
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发表时间：
1994-12-15
期刊：
影响因子：
20.3
通讯作者：
SIMMONS, PJ
中科院分区：
文献类型：
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作者：
GRONTHOS, S;GRAVES, SE;SIMMONS, PJ
单克隆抗体STRO-1鉴定成人骨髓中的克隆源性骨髓基质细胞祖细胞（成纤维细胞集落形成单位[CFU-F]）。这些STRO-1（+）CFU-F先前已显示产生具有成纤维细胞、脂肪细胞和平滑肌细胞表型的细胞。在这项研究中，测定了来自成人骨髓STRO-1（+）部分的CFU-F的成骨潜力。CFU-F通过荧光激活细胞分选从正常骨髓抽吸物中分离，基于它们的STRO-1抗原表达。通过诱导碱性磷酸酶表达、矿化基质（羟基磷灰石）的形成和骨特异性蛋白骨钙素的产生来评估成骨分化。在地塞米松存在下培养STRO-1（+）细胞（DEX; 10（-8）mol/L），抗坏血酸2-磷酸（ASC-2 P; 100 μ mol/L）和无机磷酸盐（PO4i; 2.9mmol/L），培养2周后，每个CFU中超过90%的细胞-使用骨和肝碱性磷酸酶特异性单克隆抗体，碱性磷酸酶F菌落染色阳性。碱性磷酸酶活性通过组织化学证实。在DEX、ASC-2 P和PO 4 i存在下培养4周后，在CFU-F培养物中形成矿化基质。通过光学显微镜和电子显微镜证实了矿化。经X射线衍射分析和电子色散分析证实为羟基磷灰石。放射免疫分析和北方印迹分析均显示1，25-二羟维生素D-3（10（-7）mol/L）刺激后，骨钙素释放。这项工作提供了直接证据，证明成人骨髓来源的CFU-F能够分化为功能性成骨细胞，并且STRO-1（+）群体中存在骨祖细胞。(C)1994年，美国血液学会。
The monoclonal antibody STRO-1 identifies clonogenic bone marrow stromal cell progenitors (fibroblast colony-forming units [CFU-F]) in adult human bone marrow. These STRO-1(+) CFU-F have previously been shown to give rise to cells with the phenotype of fibroblasts, adipocytes, and smooth muscle cells. In this study, the osteogenic potential of CFU-F derived from the STRO-1(+) fraction of adult human bone marrow was determined. CFU-F were isolated from normal bone marrow aspirates by fluorescence activated cell sorting, based on their expression of the STRO-1 antigen. Osteogenic differentiation was assessed by the induction of alkaline phosphatase expression, by the formation of a mineralized matrix (hydroxyapatite), and by the production of the bone-specific protein osteocalcin. STRO-1(+) cells were cultured in the presence of dexamethasone (DEX; 10(-8) mol/L), ascorbic acid 2-phosphate (ASC-2P; 100 mu mol/L), and inorganic phosphate (PO4i; 2.9 mmol/L), After 2 weeks of culture, greater than 90% of the cells in each CFU-F colony stained positive for alkaline phosphatase using a monoclonal antibody specific for bone and liver alkaline phosphatase. Alkaline phosphatase activity was confirmed by histochemistry. A mineralized matrix developed in the CFU-F cultures, after 4 weeks of culture in the presence of DEX, ASC-2P, and PO4i. Mineralization was confirmed by both light and electron microscopy. The mineral was identified as hydroxyapatite by electron dispersive x-ray microanalysis and by x-ray diffraction analysis, In replicate cultures, osteocalcin release was shown after exposure of the cells to 1,25-dihydroxyvitamin D-3 (10(-7) mol/L) both by radioimmunoassay and Northern blot analysis. This work provides direct evidence that adult human bone marrow-derived CFU-F are capable of differentiating into functional osteoblasts and that osteoprogenitors are present in the STRO-1(+) population. (C) 1994 by The American Society of Hematology.