The directional migration and differentiation of mesenchymal stem cells toward vascular endothelial cells stimulated by biphasic calcium phosphate ceramic

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 in vivo 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 in vitro and in vivo 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 in vivo implantation of porous CaP ceramics and could give some useful guidance to reveal the vascularization mechanism of the ceramics.