Predicting the therapeutic efficacy of MSC in bone tissue engineering using the molecular marker CADM1
Predicting the therapeutic efficacy of MSC in bone tissue engineering using the molecular marker CADM1
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DOI：
10.1016/j.biomaterials.2013.03.001
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发表时间：
2013-06-01
期刊：
影响因子：
14
通讯作者：
de Boer, Jan
中科院分区：
文献类型：
--
作者：
Mentink, Anouk;Hulsman, Marc;de Boer, Jan
骨髓间充质干细胞（Mesenchymal stromal cells，hMSCs）正在进入临床，但其治疗效果面临供体变异性的问题。在骨组织工程中，没有可靠的标记物已经被确定，这是能够预测骨形成能力的hMSCs植入前。为此，我们从62名供体中分离出hMSCs，并系统地表征其体外谱系分化能力、基因表达特征和体内异位骨形成能力。我们的数据证实了体外分化能力的巨大变异性，这与体内异位骨形成无关。使用DNA微阵列分析的早期传代hMSCs，我们确定了诊断骨形成分类。事实上，单个基因CADM 1与hMSC的成骨能力密切相关，可以用作可靠的体外诊断标记物。此外，与体内骨形成相关的基因表达的数据挖掘表示参与神经原性过程和Wnt信号传导。我们将应用我们的数据集来预测hMSCs的治疗效果，并在骨再生过程中获得新的见解。我们的生物信息学驱动的方法可用于细胞治疗的其他领域，以建立临床疗效的诊断标志物。(C)2013爱思唯尔有限公司保留所有权利。
Mesenchymal stromal cells (hMSCs) are advancing into the clinic but the therapeutic efficacy of hMSCs faces the problem of donor variability. In bone tissue engineering, no reliable markers have been identified which are able to predict the bone-forming capacity of hMSCs prior to implantation. To this end, we isolated hMSCs from 62 donors and characterized systematically their in vitro lineage differentiation capacity, gene expression signature and in vivo capacity for ectopic bone formation. Our data confirms the large variability of in vitro differentiation capacity which did not correlate with in vivo ectopic bone formation. Using DNA microarray analysis of early passage hMSCs we identified a diagnostic bone-forming classifier. In fact, a single gene, CADM1, strongly correlated with the bone-forming capacity of hMSCs and could be used as a reliable in vitro diagnostic marker. Furthermore, data mining of genes expressed correlating with in vivo bone formation represented involvement in neurogenic processes and Wnt signaling. We will apply our data set to predict therapeutic efficacy of hMSCs and to gain novel insight in the process of bone regeneration. Our bio-informatics driven approach may be used in other fields of cell therapy to establish diagnostic markers for clinical efficacy. (C) 2013 Elsevier Ltd. All rights reserved.