Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells
Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells
复制标题
DOI：
10.1002/bit.20250
复制
发表时间：
2004-11-05
影响因子：
3.8
通讯作者：
Li, S
中科院分区：
文献类型：
--
作者：
Park, JS;Chu, JSF;Li, S
骨髓间充质干细胞（MSCs）可以分化为多种细胞类型，包括血管平滑肌细胞（SMC），并具有作为心血管再生细胞来源的巨大潜力。我们推测，特定的血管环境因素将促进MSC分化为SMC。然而，血管力学环境对MSC的影响尚未得到表征。在这里，我们表明，机械应变调节MSC中SMC标志物的表达。循环等轴应变下调SM α-肌动蛋白和SM-22 α在MSC胶原蛋白或弹性蛋白包被的膜1天后，并减少α-肌动蛋白在应力纤维。相反，周期性单轴应变瞬时增加SM α-肌动蛋白和SM-22 α的表达1天后，随后返回到基础水平后，细胞在垂直于应变方向的方向排列。此外，单轴而非等轴应变诱导I型胶原表达的瞬时增加。DNA微阵列实验表明，单轴应变增加了SMC标志物并调节了基质分子的表达，而没有显著改变分化标志物的表达（例如，碱性磷酸酶和胶原蛋白II）。我们的研究结果表明，单轴应变，这更好地模仿SMCs所经历的机械应变的类型，可以促进MSC分化成SMCs，如果细胞的方向可以控制。该研究证明了等轴和单轴应变的差异效应，加深了我们对干细胞机械调节的理解，并为工程化MSC用于血管组织工程和再生提供了合理的基础。(C)2004 Wiley Periodicals，Inc.关键词：骨髓间充质干细胞;平滑肌细胞;机械拉伸;等轴应变;单轴应变;基因芯片
Bone marrow mesenchymal stem cells (MSCs) can differentiate into a variety of cell types, including vascular smooth muscle cells (SMCs), and have tremendous potential as a cell source for cardiovascular regeneration. We postulate that specific vascular environmental factors will promote MSC differentiation into SMCs. However, the effects of the vascular mechanical environment on MSCs have not been characterized. Here we show that mechanical strain regulated the expression of SMC markers in MSCs. Cyclic equiaxial strain downregulated SM alpha-actin and SM-22alpha in MSCs on collagen- or elastin-coated membranes after 1 day, and decreased alpha-actin in stress fibers. In contrast, cyclic uniaxial strain transiently increased the expression of SM alpha-actin and SM-22alpha after 1 day, which subsequently returned to basal levels after the cells aligned in the direction perpendicular to the strain direction. In addition, uniaxial but not equiaxial strain induced a transient increase of collagen I expression. DNA microarray experiments showed that uniaxial strain increased SMC markers and regulated the expression of matrix molecules without significantly changing the expression of the differentiation markers (e.g., alkaline phosphatase and collagen II) of other cell types. Our results suggest that uniaxial strain, which better mimics the type of mechanical strain experienced by SMCs, may promote MSC differentiation into SMCs if cell orientation can be controlled. This Study demonstrates the differential effects of equiaxial and uniaxial strain, advances our understanding of the mechanical regulation of stem cells, and provides a rational basis for engineering MSCs for vascular tissue engineering and regeneration. (C) 2004 Wiley Periodicals, Inc. Keywords: bone marrow mesenchymal stem cells; smooth muscle cells; mechanical stretch; equiaxial strain; uniaxial strain; DNA microarray