Control of smooth muscle α-actin (SMA) up-regulation in HBMSCs using remote magnetic particle mechano-activation
Control of smooth muscle α-actin (SMA) up-regulation in HBMSCs using remote magnetic particle mechano-activation
复制标题
DOI：
10.1016/j.nano.2013.06.014
复制
发表时间：
2014-01-01
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：
Hu, Bin;Dobson, Jon;El Haj, Alicia J.
物理线索有可能通过将机械刺激耦合到生化信号来引导干细胞的命运。我们假设机械刺激可以为细胞治疗应用提供一种控制方法。本研究调查了使用功能化的磁性纳米颗粒，通过暴露于时变磁场直接机械刺激血小板衍生生长因子受体α和β（PDGFR α和β），促进hBMSC向平滑肌细胞谱系分化。PDGFR α在3小时内的周期性磁机械刺激导致平滑肌α-肌动蛋白在蛋白质和mRNA水平上的表达上调。PDGFR α磷酸化响应于刺激而被检测到，并且mRNA上调通过用受体抑制剂AG 1296或中和抗体预处理细胞而被废除。我们的研究结果证明了远程控制，局部输送机械诱导分化的hBMSCs的概念，这可能在再生医学中的应用。临床编辑：使用周期性磁机械刺激器，该研究小组证明了人类骨髓源性干细胞向平滑肌蛋白表达的成功分化诱导，在再生医学中具有潜在的未来应用。(C)2014爱思唯尔公司All rights reserved.
Physical cues have the potential to guide stem cell fate by coupling a mechanical stimulus to biochemical signaling. We have postulated that mechanical stimulation could provide a control method for cell therapy applications. This study investigates the use of functionalized magnetic nanoparticles to promote hBMSC differentiation towards a smooth muscle cell lineage by direct mechanical stimulation of platelet-derived growth factor receptor a and beta ( PDGFR alpha and beta) via exposure to time-varying magnetic fields. Cyclical magneto-mechanical stimulation of PDGFR alpha over a 3 h period results in up-regulation of smooth muscle alpha-actin expression in both protein and mRNA level. PDGFR alpha phosphorylation is detected in response to stimulation and the mRNA up-regulation is abrogated by pretreatment of cells with a receptor inhibitor, AG1296 or the neutralization antibody. Our results demonstrate proof of concept for remote controlled, locally-delivered mechanically induced differentiation of hBMSCs which could have applications in regenerative medicine. From the Clinical Editor: Using a cyclical magneto-mechanical stimulator, this team of investigators demonstrated successful differentiation induction of human bone marrow-derived stem cells toward smooth muscle protein expression, with potential future applications in regenerative medicine. (C) 2014 Elsevier Inc. All rights reserved.