Fibroblast morphogenesis on 3D collagen matrices: the balance between cell clustering and cell migration.
Fibroblast morphogenesis on 3D collagen matrices: the balance between cell clustering and cell migration.
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DOI：
10.1016/j.yexcr.2013.05.003
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发表时间：
2013-10-01
影响因子：
3.7
通讯作者：
Grinnell, Frederick
中科院分区：
文献类型：
--
作者：
da Rocha-Azevedo, Bruno;Grinnell, Frederick
关键词：
成纤维细胞簇已在各种情况下的组织中观察到：在纤维化和瘢痕中，在毛囊毛乳头的形成中，以及作为发育期间发生的间充质凝结的一般过程的一部分。细胞聚集已被证明取决于细胞外基质的特征、生长因子环境和稳定细胞-细胞相互作用的机制。体外研究表明，相对于细胞-基质粘附，增加细胞-细胞粘附的可能性促进细胞聚集。研究成纤维细胞聚集的实验模型利用了离心、悬滴和具有较差粘附性、柔软和机械不稳定性质的基质。在这篇综述中，我们总结了一个新的，高度听话的，细胞聚集的研究模型中，人成纤维细胞在胶原蛋白基质的表面上孵育的工作。成纤维细胞聚集在促收缩生长因子条件下发生（例如，血清或血清脂质激动剂溶血磷脂酸），但在促迁移生长因子条件下（例如，血小板衍生生长因子），并可通过转换生长因子环境来逆转。细胞收缩在使细胞更紧密地聚集在一起和刺激细胞将纤连蛋白组织成纤维状基质中起双重作用。成纤维细胞与共享的纤连蛋白原纤维基质的结合稳定了簇，并且当生长因子条件被切换以促进细胞分散时发生原纤维基质的片段化。
Fibroblast clusters have been observed in tissues under a variety of circumstances: in fibrosis and scar, in the formation of hair follicle dermal papilla, and as part of the general process of mesenchymal condensation that takes place during development. Cell clustering has been shown to depend on features of the extracellular matrix, growth factor environment, and mechanisms to stabilize cell-cell interactions. In vitro studies have shown that increasing the potential for cell-cell adhesion relative to cell-substrate adhesion promotes cell clustering. Experimental models to study fibroblast clustering have utilized centrifugation, hanging drops, and substrata with poorly adhesive, soft and mechanically unstable properties. In this review, we summarize work on a new, highly tractable, cell clustering research model in which human fibroblasts are incubated on the surfaces of collagen matrices. Fibroblast clustering occurs under procontractile growth factor conditions (e.g., serum or the serum lipid agonist lysophosphatidic acid) but not under promigratory growth factor conditions (e.g., platelet-derived growth factor) and can be reversed by switching growth factor environments. Cell contraction plays a dual role in clustering to bring cells closer together and to stimulate cells to organize fibronectin into a fibrillar matrix. Binding of fibroblasts to a shared fibronectin fibrillar matrix stabilizes clusters, and fragmentation of the fibrillar matrix occurs when growth factor conditions are switched to promote cell dispersal.
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