Tuning intercellular cues to regulate paracrine secretion for enhanced neovascularization

创造功能性组织和器官移植物的一个主要挑战是产生功能性血管。这是一个被称为血管化的过程。间充质干细胞(MSCs)可指导体内骨骼组织的修复，并分泌多种可能促进血管生成的生长因子。这个项目的总体目标是设计MSC培养来分泌这些因素。该项目团队有初步数据表明，细胞间的黏附增加了这种分泌。这种增强的机制将被研究，以制定血管化工程化或受损组织的设计规则。该项目还将为K-12女性和代表性不足的群体提供实践机会。该项目将探索细胞间黏附作为促进工程组织或受损组织中血管形成的设计参数。细胞间黏附和黏附蛋白神经钙粘附素(N-钙粘素)似乎调节促进这种形成的因子的分泌。研究将量化MSC分泌谱、N-钙粘素输入和潜在的N-钙粘素介导、机械转导和生化信号之间的联系。目的是建立细胞间黏附、力传导、生化信号和旁分泌特征之间的定量联系。如果成功，结果将解决功能三维组织工程组装的主要障碍。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.