Center for Biomaterials, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea.
Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Republic of Korea.
ACS Appl Mater Interfaces. 2022 Sep 14;14(36):40522-40534. doi: 10.1021/acsami.2c07952. Epub 2022 Aug 29.
The mechanism by which stromal cells fill voids in injured tissue remains a fundamental question in regenerative medicine. While it is well-established that fibroblasts fill voids by depositing extracellular matrix (ECM) proteins as they migrate toward the wound site, little is known about their ability to adopt an epithelial-like purse-string behavior. To investigate fibroblast behavior during gap closure, we created an artificial wound with a large void space. We discovered that fibroblasts could form a free-standing bridge over deep microvoids, closing the void via purse-string contraction, a mechanism previously thought to be unique to epithelial wound closure. The findings also revealed that myosin II mediated contractility and intercellular adherent junctions were required for the closure of the fibroblast gap in our fabricated three-dimensional artificial wound. To fulfill their repair function under the specific microenvironmental conditions of wounds, fibroblasts appeared to acquire the structural features of epithelial cells, namely, contractile actin bundles that span over multiple cells along the boundary. These findings shed light on a novel mechanism by which stromal cells bridge the 3D gap during physiological processes such as morphogenesis and wound healing.
基质细胞如何填充受损组织中的空隙仍然是再生医学中的一个基本问题。虽然已经证实成纤维细胞通过在向伤口部位迁移时沉积细胞外基质 (ECM) 蛋白来填充空隙，但对于它们采用类似上皮的荷包缝合行为的能力知之甚少。为了研究成纤维细胞在间隙闭合过程中的行为，我们在人工伤口中制造了一个大的空隙。我们发现，成纤维细胞可以在深微空隙上形成一个独立的桥，通过荷包缝合收缩来闭合空隙，这是一种以前被认为是上皮伤口闭合所特有的机制。研究结果还表明，肌球蛋白 II 介导的收缩性和细胞间黏附连接对于我们在三维人工伤口中闭合成纤维细胞间隙是必需的。为了在伤口的特定微环境条件下发挥其修复功能，成纤维细胞似乎获得了上皮细胞的结构特征，即跨越多个细胞沿着边界延伸的收缩性肌动蛋白束。这些发现揭示了基质细胞在形态发生和伤口愈合等生理过程中桥接 3D 间隙的一种新机制。
