Immobilized Jagged1 for Notch3-specific Differentiation and Phenotype Control of Vascular Smooth Muscle Cells
Abstract
Notch signaling plays a critical role in regulating vascular morphogenesis. In vascular interventions, the endothelial cells (ECs) are often damaged, and EC-SMC contact is compromised. The objective of this study was to investigate if immobilized Jagged1 can act as an EC-surrogate material to direct and control vascular smooth muscle cell (VSMC) behavior via Notch signaling. It was shown that immobilized Jagged1 induced vascular differentiation of iPSC-derived mesenchymal stem cells and mouse embryonic multipotent cells. Immobilized Jagged1 was insufficient to induce mature contractile markers in coronary artery SMCs; therefore, serum starvation and TGFβ1 treatment were investigated. Although Notch signaling is mechanosensitive in nature, it was also determined that a pulling force was not needed for Notch3 activation. Overall, it is concluded that immobilized Jagged1 is an essential regulator in SMC phenotype and SMC differentiation. These findings may have clinical relevance for modulating VSMC phenotype in cardiovascular disease states and in tissue engineering.