Thickness sensing of hMSCs on collagen gel directs stem cell fate
Thickness sensing of hMSCs on collagen gel directs stem cell fate
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DOI：
10.1016/j.bbrc.2010.09.052
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发表时间：
2010-10-15
影响因子：
3.1
通讯作者：
Tan, Lay Poh
中科院分区：
文献类型：
--
作者：
Leong, Wen Shing;Tay, Chor Yong;Tan, Lay Poh
机械顺应性基质为多能干细胞提供了重要的生物力学线索，以调节细胞命运，如分化，增殖和维持其表型。细胞感知的有效模量不仅取决于基底的固有力学性能，还与基底的厚度有关。从我们的研究中发现，来自数百微米远的底层刚性支撑的干扰可以诱导显著的细胞反应。将人骨髓间充质干细胞（hMSCs）培养在顺应性生物凝胶I型胶原上。不同的厚度，但相同的ECM成分和局部刚度。细胞感觉到薄凝胶（130 μ m）比厚凝胶（1440 μ m）具有更高的有效模量，这反映在它们的形态、肌动蛋白纤维结构、增殖和组织特异性基因表达的变化中。仅在薄凝胶上观察到向神经元谱系的定型。相反，厚凝胶（1440 μ m）被发现像一个基板具有较低的有效模量，抑制肌动蛋白纤维聚合。厚基质上的干细胞不表达组织特异性基因，保持静止状态。这项研究强调了在细胞反应的调制过程中，不仅需要考虑局部模量，还需要考虑生物聚合物凝胶涂层的厚度。(C)2010年爱思唯尔公司All rights reserved.
Mechanically compliant substrate provides crucial biomechanical cues for multipotent stem cells to regulate cellular fates such as differentiation, proliferation and maintenance of their phenotype. Effective modulus of which cells sense is not only determined by intrinsic mechanical properties of the substrate, but also the thickness of substrate. From our study, it was found that interference from underlying rigid support at hundreds of microns away could induce significant cellular response. Human mesenchymal stem cells (hMSCs) were cultured on compliant biological gel, collagen type I. of different thickness but identical ECM composition and local stiffness. The cells sensed the thin gel (130 mu m) as having a higher effective modulus than the thick gel (1440 mu m) and this was reflected in their changes in morphology, actin fibers structure, proliferation and tissue specific gene expression. Commitment into neuronal lineage was observed on the thin gel only. Conversely, the thick gel (1440 mu m) was found to act like a substrate with lower effective modulus that inhibited actin fiber polymerization. Stem cells on the thick substrate did not express tissue specific genes and remained at their quiescent state. This study highlighted the need to consider not only the local modulus but also the thickness of biopolymer gel coating during modulation of cellular responses. (C) 2010 Elsevier Inc. All rights reserved.