Tuning intercellular cues to regulate paracrine secretion for enhanced neovascularization

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A major challenge to creating functional tissue and organ grafts is generating functional blood vessels. This is a process called vascularization. Mesenchymal stem cells (MSCs) direct the repair of skeletal tissue in the body and secrete many growth factors that might promote vascularization. The overall goal of this project is to engineer MSC cultures to secrete these factors. The project team has preliminary data indicating that cell-to-cell adhesion increases that secretion. The mechanism of that enhancement will be investigated to develop design rules for vascularizing engineered or damaged tissues. The project will also deliver hands-on opportunities to K-12 women and underrepresented groups.This project will explore intercellular adhesion as a design parameter for promoting blood vessel formation in engineered or damaged tissues. Intercellular adhesion, and the adhesion protein, neural cadherin (N-cadherin), appear to regulate the secretion of factors that promote such formation. Studies will quantify links between MSC secretion profiles, N-cadherin inputs, and the underlying N-cadherin-mediated, mechano-transduction and biochemical signaling. The objective is to establish quantitative links between intercellular adhesion, force transduction, biochemical signaling, and paracrine secretion profiles. If successful, the results would address a major roadblock towards the engineered assembly of functional, three-dimensional tissues.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.