Mechanical stimulation induces morphological and phenotypic changes in bone marrow-derived progenitor cells within a three-dimensional fibrin matrix
Mechanical stimulation induces morphological and phenotypic changes in bone marrow-derived progenitor cells within a three-dimensional fibrin matrix
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DOI：
10.1002/jbm.a.31041
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发表时间：
2007-06-01
影响因子：
4.9
通讯作者：
Vorp, David A.
中科院分区：
文献类型：
--
作者：
Nieponice, Alejandro;Maul, Timothy M.;Vorp, David A.
组织工程的主要限制之一是细胞来源。多能祖细胞似乎具有许多用于该目的的有希望的特征。已知机械刺激在决定细胞表型方面起重要作用。本工作的目的是研究周期性拉伸对大鼠骨髓来源的祖细胞（BMPC）的形态和平滑肌定向分化的三维纤维蛋白基质中的影响。将BMPC悬浮在纤维蛋白凝胶中，移液到Flexcell（TM）Tissue-Train（TM）板的槽中，并用10%的纵向循环拉伸以Hz刺激6天。将无约束（无应力和应变）和静态锚定（受约束但未拉伸）样本用作对照。与静态锚定和自由浮动对照相比，拉伸样品中每个细胞的应力细丝面积增加。自由浮动对照中的细胞随机排列，而在其他组中它们平行于应力或应变的方向排列。免疫荧光表明，增加表达的平滑肌标志物（平滑肌肌动蛋白和h1-钙调蛋白）在拉伸和约束的控制样品，但不受约束的控制。定性评估表明，在两种机械刺激的样品中，胶原蛋白的产生增加。与约束对照相比，拉伸样品中的增殖受到抑制。这项工作表明大鼠BMPC在三维模型中暴露于生物力学刺激时向平滑肌细胞样谱系分化的所有能力。约束样品引起BMPC变化的观察结果表明，单独的应力可能是刺激性的，但添加循环拉伸似乎增加了反应。(C)2006 Wiley Periodicals，Inc. J Biomed Mater Res 81 A：523-530，2007.
One of the major limitations in tissue engineering is cell sourcing. Multipotent progenitor cells appear to have many promising features for that purpose. Mechanical stimulation is known to play an important role iii determining cell phenotype. The aim of this work was to investigate the effects of cyclic stretch on rat bone marrow derived progenitor cell (BMPC) morphology and smooth muscle-directed differentiation within a three-dimensional fibrin matrix. BMPCs were suspended in a fibrin gel, pipetted into the trough of Flexcell (TM) Tissue-Train (TM) plates, and stimulated with 10%, longitudinal cyclic stretch at Hz for 6 days. Unconstrained (stress- and strain-free) and static anchored (constrained but not stretched) samples were used as controls. Stress filament area per cell was increased in the stretched samples compared to static anchored and free-float controls. Cells in the free float controls were randomly aligned, while they aligned parallel to the direction of the stress or strain in the other groups. Immunofluorescence suggested an increased expression of smooth muscle markers (smooth muscle of actin and h1-calponin) in both stretched and constrained control samples, but not in unconstrained controls. Qualitative assessment suggested that collagen production was increased hi both mechanically stimulated samples. Proliferation was inhibited in stretched samples compared to the constrained controls. This work suggests aii ability of rat BMPCs to differentiate toward a smooth-muscle-cell-like lineage when exposed to biomechanical stimulation in a three-dimensional model. The observation that the constrained samples induced changes in BMPCs suggests that stress alone may be stimulatory, but addition of cyclic stretch appears to augment the responses. (C) 2006 Wiley Periodicals, Inc. J Biomed Mater Res 81A: 523-530, 2007.