Identifying a Molecular Phenotype for Bone Marrow Stromal Cells With In Vivo Bone-Forming Capacity
Identifying a Molecular Phenotype for Bone Marrow Stromal Cells With In Vivo Bone-Forming Capacity
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DOI：
10.1359/jbmr.091018
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发表时间：
2010-04-01
影响因子：
6.2
通讯作者：
Kassem, Moustapha
中科院分区：
文献类型：
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作者：
Larsen, Kenneth H.;Frederiksen, Casper M.;Kassem, Moustapha
骨髓基质细胞(BMSCs)分化为成骨细胞的能力正被开发用于基于细胞的修复骨缺损的治疗。然而，体外培养的BMSCs的表型预测其成骨能力尚不清楚。因此，我们使用DNA微阵列比较了两个人骨髓基质细胞(HBMSC)群体。一种是体内异位成骨(hBMSC-TERT+bone)，另一种是不能(hBMSC-TERT-bone)。与hBMSC-TERT-bone相比，hBMSC-TERT+bone细胞高表达细胞外基质基因(17%比5%)，在其启动子区域预测SP3转录因子结合位点的基因比例更高(21%比8%)。另一方面，hBMSC-TERT-bone细胞表达更多的免疫反应相关基因(26%比8%)。为了检验这些标志物的预测价值，我们研究了它们在6个不同的hBMSC克隆中的表达水平与体内成骨能力的相关性。结果发现核心蛋白聚糖、赖氨酰氧化酶样4、利钠肽受体C和四联素的表达水平显著相关，而与成骨细胞标志物Runx2、碱性磷酸酶、I型胶原、骨桥蛋白和骨涎蛋白的表达水平无显著正相关。我们的数据表明，体外分子标记预测hBMSCs在体内的成骨能力，识别更多的这些预测标记将在用于治疗之前的成骨细胞质量控制中非常有用。(C)2010年美国骨与矿物研究学会。
The ability of bone marrow stromal cells (BMSCs) to differentiate into osteoblasts is being exploited in cell-based therapy for repair of bone defects. However, the phenotype of ex vivo cultured BMSCs predicting their bone-forming capacity is not known. Thus we employed DNA microarrays comparing two human bone marrow stromal cell (hBMSC) populations. One is capable of in vivo heterotopic bone formation (hBMSC-TERT+Bone), and the other is not (hBMSC-TERT-Bone). Compared with hBMSC-TERT-Bone, the hBMSC-TERT+Bone cells had an increased overrepresentation of extracellular matrix genes (17% versus 5%) and a larger percentage of genes with predicted SP3 transcription factor-binding sites in their promoter region (21% versus 8%) On the other hand, hBMSC-TERT-Bone cells expressed a larger number of immune-response-related genes (26% versus 8%). In order to test for the predictive value of these markers, we studied the correlation between their expression levels in six different hBMSC-derived clones and the ability to form bone in vivo We found a significant correlation for decorin, lysyl oxidase-like 4, natriuretic peptide receptor C, and tetranectin No significant positive correlation was found for canonical osteoblastic markers Runx2, alkaline phosphatase, collagen type I, osteopontin, and bone sialoprotein Prospective isolation of four additional hBMSC clones based on their expression levels of the molecular markers correlated with their in vivo bone-formation ability In conclusion, our data suggest an in vitro molecular signature predictive for hBMSCs' in vivo bone-formation ability Identifying more of these predictive markers would be very useful in the quality control of osteoblastic cells before use in therapy. (C) 2010 American Society for Bone and Mineral Research.