The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces
The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces
复制标题
DOI：
10.1002/term.2263
复制
发表时间：
2017-12-01
影响因子：
3.3
通讯作者：
Rolauffs, Bernd
中科院分区：
文献类型：
--
作者：
Uynuk-Ool, Tatiana;Rothdiener, Miriam;Rolauffs, Bernd
控制间充质基质细胞（MSC）的形状是一种研究和指导MSC体外行为的新方法。假设可以通过使用刚度限定的生物材料表面和通过施加循环张力来产生特定的MSC形状。使用的生物材料是薄和厚的硅胶片、纤连蛋白涂层和压实的I型胶原蛋白片。通过描述尺寸和膜突起的形状描述符来量化MSC形态。通过原子力显微镜和定量逆转录聚合酶链反应的平滑肌细胞（SMC）标记基因（ACTA 2，TAGLN，CNN1）的表达，纳米尺度的刚度进行了测量。以2.5%或5%的振幅施加循环拉伸。与刚度较低的生物材料相比，与刚度较高的生物材料的附着产生了更多的细长MSC，具有更少的膜突起。对于循环拉伸，选择压实的胶原蛋白片，其与所有研究的生物材料中最长的MSC形状相关。如所预期的，周期性拉伸在拉伸期间延长MSC。然而，在停止拉伸后一小时，MSC形状再次变圆，表明拉伸诱导的形状丧失。不同的形状描述符值获得不同的拉伸制度与SMC标记基因的表达水平显着相关。约0.4的圆度值和3.4的纵横比对于ACTA 2和CNN1的最高表达水平是关键的。因此，可以使用生物材料相关的刚度和张力生成的特定形状描述符值可以用作诱导MSC中特定基因表达水平的模板。版权所有（c）2017约翰威利父子有限公司
Controlling mesenchymal stromal cell (MSC) shape is a novel method for investigating and directing MSC behaviour in vitro. it was hypothesized that specifigc MSC shapes can be generated by using stiffness-defined biomaterial surfaces and by applying cyclic tensile forces. Biomaterials used were thin and thick silicone sheets, fibronectin coating, and compacted collagen type I sheets. The MSC morphology was quantified by shape descriptors describing dimensions and membrane protrusions. Nanoscale stiffness was measured by atomic force microscopy and the expression of smooth muscle cell (SMC) marker genes (ACTA2, TAGLN, CNN1) by quantitative reverse-transcription polymerase chain reaction. Cyclic stretch was applied with 2.5% or 5% amplitudes. Attachment to biomaterials with a higher stiffness yielded more elongated MSCs with fewer membrane protrusions compared with biomaterials with a lower stiffness. For cyclic stretch, compacted collagen sheets were selected, which were associated with the most elongated MSC shape across all investigated biomaterials. As expected, cyclic stretch elongated MSCs during stretch. One hour after cessation of stretch, however, MSC shape was rounder again, suggesting loss of stretch-induced shape. Different shape descriptor values obtained by different stretch regimes correlated significantly with the expression levels of SMC marker genes. Values of approximately 0.4 for roundness and 3.4 for aspect ratio were critical for the highest expression levels of ACTA2 and CNN1. Thus, specific shape descriptor values, which can be generated using biomaterial-associated stiffness and tensile forces, can serve as a template for the induction of specific gene expression levels in MSC. Copyright (c) 2017 John Wiley & Sons, Ltd.