Tuning intercellular cues to regulate paracrine secretion for enhanced neovascularization

调整细胞间信号以调节旁分泌分泌以增强新血管形成

• 批准号: 2229523
• 负责人: Deborah Leckband
• 金额: $ 56.52万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2229523&HistoricalAwards=false
• 关键词: Tuning; intercellular; cues; regulate; paracrine

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.

制造功能性组织和器官移植物的主要挑战是生成功能性血管。这个过程叫做血管化。间充质干细胞（MSCs）指导体内骨骼组织的修复，并分泌许多可能促进血管形成的生长因子。该项目的总体目标是设计MSC培养物以分泌这些因子。该项目小组的初步数据表明，细胞与细胞的粘附增加了这种分泌。这种增强的机制将被研究，以开发用于血管化工程组织或受损组织的设计规则。 该项目还将为K-12妇女和代表性不足的群体提供实践机会。该项目将探索细胞间粘附作为促进工程组织或受损组织中血管形成的设计参数。细胞间粘附和粘附蛋白，神经钙粘蛋白（N-钙粘蛋白），似乎调节促进这种形成的因子的分泌。 研究将量化MSC分泌概况，N-钙粘蛋白输入，和潜在的N-钙粘蛋白介导的，机械转导和生化信号之间的联系。其目的是建立定量的细胞间粘附，力转导，生化信号，和旁分泌的档案之间的联系。如果成功的话，该成果将解决一个主要的障碍，走向工程组装的功能，三维tissues.This奖项反映了NSF的法定使命，并已被认为是值得的支持，通过评估使用基金会的智力价值和更广泛的影响审查标准。