Unmet Need:
In recent decades, postnatal vasculogenesis has been considered to be an important mechanism for neovascularization via circulating endothelial progenitor cells (EPCs) derived from marrow. Since then, EPCs have been proposed as a potential tool for treating vascular disease, either through infusion to the site of vascularization or ex vivo expansion for engineering vascularized tissue constructs. Understanding the molecular mechanism that regulates neovascularization by EPCs will provide insights for therapeutic vascularization.
Technology Overview:
Researchers at Johns Hopkins have developed a chemically and mechanically tunable hydrogel to study tube morphogenesis in vitro and have demonstrated that vascular endothelial growth factor (VEGF) and substrate mechanics co-regulate tubulogenesis of EPCs. Studies conducted showed that high levels of VEGF initiate tube morphogenesis and activate activate matrix metalloproteinases (MMPs) for EPC migration. Additionally, membrane type 1 –MMP (MT1-MMP) is required to enable the movement of EPCs on the matrix and that EPCs sense matrix stiffness through signaling cascades leading to the activation of the RhoGTPase Cdc42.
