Chen Ying, Wang Jing, Zhu Xiangdong, Chen Xuening, Yang Xiao, Zhang Kai, Fan Yujiang, Zhang Xingdong
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
Regen Biomater. 2018 Jun;5(3):129-139. doi: 10.1093/rb/rbx028. Epub 2017 Oct 31.
Osteoinductivity of porous calcium phosphate (CaP) ceramics has been widely investigated and confirmed, and it might be attributed to the rapid formation of the vascular networks after implantation of the ceramics. In this study, to explore the vascularization mechanism within the CaP ceramics, the migration and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) under the stimulation of porous biphasic calcium phosphate (BCP) ceramic with excellent osteoinductivity were systematically investigated. The results indicated that the directional migration of BMSCs toward BCP ceramic occurred when evaluated by using a transwell model, and the BMSCs migration was enhanced by the seeded macrophages on the ceramic in advance. Besides, by directly culturing BMSCs on BCP ceramic discs under both and physiological environment, it was found that the differentiation of BMSCs toward vascular endothelial cells (VECs) happened under the stimulation of BCP ceramic, as was confirmed by the up-regulated gene expressions and protein secretions of VECs-related characteristic factors, including kinase insert domain receptor, von willebrand factor, vascular cell adhesion molecule-1 and cadherin 5 in the BMSCs. This study offered a possibility for explaining the origin of VECs during the rapid vascularization process after implantation of porous CaP ceramics and could give some useful guidance to reveal the vascularization mechanism of the ceramics.
多孔磷酸钙(CaP)陶瓷的骨诱导性已得到广泛研究和证实,这可能归因于陶瓷植入后血管网络的快速形成。在本研究中,为了探究CaP陶瓷内部的血管化机制,系统研究了具有优异骨诱导性的多孔双相磷酸钙(BCP)陶瓷刺激下骨髓间充质干细胞(BMSCs)的迁移和分化。结果表明,使用transwell模型评估时,BMSCs向BCP陶瓷发生定向迁移,预先接种在陶瓷上的巨噬细胞可增强BMSCs的迁移。此外,通过在生理环境和非生理环境下直接将BMSCs培养在BCP陶瓷盘上,发现BCP陶瓷刺激下BMSCs向血管内皮细胞(VECs)分化,这通过BMSCs中VECs相关特征因子(包括激酶插入结构域受体、血管性血友病因子、血管细胞黏附分子-1和钙黏蛋白5)的基因表达上调和蛋白分泌得到证实。本研究为解释多孔CaP陶瓷植入后快速血管化过程中VECs的来源提供了一种可能性,并可为揭示陶瓷的血管化机制提供一些有用的指导。