AO Research Institute Davos, Clavadelerstrasse 8, Davos Platz, Switzerland.
Eur Cell Mater. 2011 Oct 11;22:214-25. doi: 10.22203/ecm.v022a17.
There is great interest in how bone marrow derived stem cells make fate decisions. Numerous studies have investigated the role of individual growth factors on mesenchymal stem cell differentiation, leading to protocols for cartilage, bone and adipose tissue. However, these protocols overlook the role of biomechanics on stem cell differentiation. There have been various studies that have applied mechanical stimulation to constructs containing mesenchymal stem cells, with varying degrees of success. One critical fate decision is that between cartilage and bone. Articular motion is a combination of compressive, tensile and shear deformations; therefore, one can presume that compression alone is unlikely to be a sufficient mechanical signal to generate a cartilage-like tissue in vitro. Within this study, we aimed to determine the role of shear on the fate of stem cell differentiation. Specifically, we investigated the potential enhancing effect of surface shear, superimposed on cyclic axial compression, on chondrogenic differentiation of human bone marrow-derived stem cells. Using a custom built loading device we applied compression, shear or a combination of both stimuli onto fibrin/polyurethane composites in which human mesenchymal stem cells were embedded, while no exogenous growth-factors were added to the culture medium. Both compression or shear alone was insufficient for the chondrogenic induction of human mesenchymal stem cells. However, the application of shear superimposed upon dynamic compression led to significant increases in chondrogenic gene expression. Histological analysis detected sulphated glycosaminoglycan and collagen II only in the compression and shear group. The results obtained may provide insight into post-operative care after cell therapy involving mesenchymal stromal cells.
人们对于骨髓来源的干细胞如何做出命运抉择非常感兴趣。许多研究已经调查了单个生长因子对间充质干细胞分化的作用，从而制定了用于软骨、骨和脂肪组织的方案。然而，这些方案忽略了生物力学对干细胞分化的作用。已经有许多研究对含有间充质干细胞的构建体施加机械刺激，取得了不同程度的成功。一个关键的命运抉择是软骨和骨之间的抉择。关节运动是压缩、拉伸和剪切变形的组合；因此，可以假定仅压缩不太可能成为在体外产生类软骨组织的充分机械信号。在本研究中，我们旨在确定剪切对干细胞分化命运的作用。具体来说，我们研究了表面剪切在循环轴向压缩之上对人骨髓来源干细胞向软骨分化的潜在增强作用。我们使用定制的加载装置将压缩、剪切或两者的组合施加到纤维蛋白/聚氨酯复合材料上，其中嵌入了人间充质干细胞，而培养介质中未添加外源性生长因子。单独压缩或剪切都不足以诱导人骨髓间充质干细胞的软骨生成。然而，在动态压缩之上施加剪切会导致软骨形成基因表达的显著增加。组织学分析仅在压缩和剪切组中检测到硫酸化糖胺聚糖和胶原 II。所获得的结果可能为涉及间充质基质细胞的细胞治疗后的术后护理提供一些见解。
