Remote regulation of magnetic particle targeted Wnt signaling for bone tissue engineering
Remote regulation of magnetic particle targeted Wnt signaling for bone tissue engineering
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DOI：
10.1016/j.nano.2017.09.008
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发表时间：
2018-01-01
影响因子：
5.4
通讯作者：
El Haj, Alicia J.
中科院分区：
文献类型：
--
作者：
Rotherham, Michael;Henstock, James R.;El Haj, Alicia J.
Wnt信号传导在人间充质干细胞（hMSC）的分化中起关键作用。因此，Wnt蛋白具有相当大的治疗价值，但价格昂贵且难以生产。UM 206是Wnt受体Frizzled的合成肽和配体。将UM 206连接到磁性纳米颗粒（MNP）上，可以使用磁场操纵配体-MNP复合物，从而控制卷曲刺激。使用这种方法，在hMSC中激活Wnt信号传导，这导致卷曲成簇、β-连环蛋白易位和TCF/LEF应答性转录的激活。在骨生成过程中，UM 206-MNP启动局部矿化基质形成。在离体鸡股骨中注射和磁刺激UM 206-MNP标记的MSC导致矿化增加，其与添加骨形态发生蛋白2（BMP 2）释放微粒协同作用。由于这有助于对信号转导的外部控制，缀合的MNP技术具有作为研究工具和用于调节临床细胞疗法中的组织形成的应用。(C)2017爱思唯尔公司All rights reserved.
Wnt signaling is critically involved in the differentiation of human Mesenchymal Stem Cells (hMSC). Wnt proteins therefore have considerable therapeutic value, but are expensive and difficult to produce. UM206 is a synthetic peptide and ligand for the Wnt receptor Frizzled. Attachment of UM206 to magnetic nanoparticles (MNP) enables the ligand-MNP complex to be manipulated using magnetic fields, allowing control of Frizzled stimulation. Using this approach, Wnt signaling was activated in hMSC which resulted in Frizzled clustering, beta-catenin translocalization and activation of TCF/LEF responsive transcription. During osteogenesis, UM206-MNP initiated localized mineralized matrix formation. Injection and magnetic stimulation of UM206-MNP-labeled MSC in ex vivo chick femurs resulted in increased mineralization which acted synergistically with addition of bone morphogenic protein 2 (BMP2) releasing micro-particles. As this facilitates external control over signal transduction, conjugated MNP technology has applications both as a research tool and for regulating tissue formation in clinical cell therapies. (C) 2017 Elsevier Inc. All rights reserved.