Bioengineering Tracheas Through Targeting Activated CD47

描述（由申请人提供）：气管丢失是一种毁灭性的疾病，气管仍然是剩余的重要器官之一，没有足够的替代品。人工合成气管支架或去细胞气管支架的工程气管移植的尝试取得了有限的成功，包括长期和充满并发症的二次愈合和灾难性的气管管腔塌陷。本提案将研究新发现的信号通路及其在限制细胞和组织再生、植入和气管血管生成中所起的作用。从我们独特的小鼠原位气管移植模型实验中获得的知识将转化为产生功能性“准备就绪”的人类气管。

DESCRIPTION (provided by applicant): Tracheal loss is a devastating condition and the trachea remains one of the remaining vital organs for which there is no adequate substitute. Attempts at engineering tracheal transplants from either synthetic constructs or decellularized tracheal scaffolds have met with limited success including long and complication-filled secondary healing and catastrophic tracheal luminal collapse. This proposal will investigate newly identified signaling pathways and the role that they play in limiting cellular and tissue regeneration, engraftment and tracheal angiogenesis. Knowledge gained from experiments in our unique murine model of orthotopic tracheal transplant will be translated into generating a functional "shovel-ready" human trachea.