Mesenchymal stem cell durotaxis depends on substrate stiffness gradient strength.
Mesenchymal stem cell durotaxis depends on substrate stiffness gradient strength.
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DOI：
10.1002/biot.201200205
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发表时间：
2013-04
影响因子：
4.7
通讯作者：
Engler, Adam J.
中科院分区：
文献类型：
--
作者：
Vincent, Ludovic G.;Choi, Yu Suk;Alonso-Latorre, Baldomero;del Alamo, Juan C.;Engler, Adam J.
间充质干细胞（MSCs）对生态位弹性有反应，这在组织之间和组织内部是不同的。僵硬梯度是由病理条件引起的，但也可以通过正常的变化发生，例如肌肉。即使在分化之前，MSCs也会响应浅刚度梯度进行定向迁移。需要更精细的刚度范围和强度梯度来更好地理解正常和疾病病理中迁移的机械调节。我们使用三种不同的系统来描述聚丙烯酰胺刚度梯度制造，这些系统产生生理（1 Pa/µm）、病理（10 Pa/µm）和阶跃（≥100Pa/um）强度梯度，跨越大多数软组织的生理相关刚度，即1 - 12 kPa。在每个梯度下，msc迁移到最硬的区域。延时显微镜显示，迁移速度与梯度强度成正比。在收缩激动剂溶血磷脂酸（LPA）和细胞骨骼干扰药物诺可达唑和细胞松弛素的存在下，定向迁移减少；LPA和nocodazole处理的细胞仍然呈扩散和突出，而细胞松弛素处理的细胞则没有。未处理和诺可达唑处理的细胞以相似的方式扩散，但诺可达唑处理的细胞的牵引力大大减弱。这些数据表明，肌动蛋白是迁移所必需的，而微管是定向迁移所必需的。这些数据还表明，在体内，间充质干细胞可能对更硬的区域的修复有更大的贡献，它们可能优先积聚在那里。
Mesenchymal stem cells (MSCs) respond to niche elasticity, which varies between and within tissues. Stiffness gradients result from pathological conditions but also occur through normal variation, e.g. muscle. MSCs undergo directed migration even in response to shallow stiffness gradients before differentiating. More refined gradients of both stiffness range and strength are needed to better understand mechanical regulation of migration in normal and disease pathologies. We describe polyacrylamide stiffness gradient fabrication using three distinct systems that generate stiffness gradients of physiological (1 Pa/µm), pathological (10 Pa/µm), and step (≥ 100Pa/um) strength spanning physiologically relevant stiffness for most soft tissue, i.e. 1–12 kPa. MSCs migrated to the stiffest region for each gradient. Time-lapse microscopy revealed that migration velocity scaled directly with gradient strength. Directed migration was reduced in the presence of the contractile agonist lysophosphatidic acid (LPA) and cytoskeletal-perturbing drugs nocodazole and cytochalasin; LPA- and nocodazole-treated cells remained spread and protrusive, while cytochalasin-treated cells did not. Untreated and nocodazole-treated cells spread in a similar manner, but nocodazole-treated cells had greatly diminished traction forces. These data suggest that actin is required for migration whereas microtubules are required for directed migration. The data also imply that in vivo, MSCs may have a more significant contribution to repairs in stiffer regions where they may preferentially accumulate.
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影响因子：
7.7
作者：
Holle, Andrew W.;Engler, Adam J.
通讯作者：
Engler, Adam J.
DOI：
10.1002/ar.b.20081
发表时间：
2005-11-01
期刊：
Anatomical Record Part B:The New Anatomist
影响因子：
--
作者：
Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
DOI：
10.1126/science.1176009
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hynes RO
通讯作者：
Hynes RO
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW
影响因子：
3.4
作者：
Byfield, Fitzroy J.;Wen, Qi;Janmey, Paul A.
通讯作者：
Janmey, Paul A.