Synthetic circuits for therapeutic platelet production and immunomodulation

项目摘要 中性粒细胞被迅速募集到感染和损伤部位，形成抵御入侵的第一道防线。 病原体或组织损伤，并在炎症的发生和发展中发挥重要作用， 反应然而，一旦病原体被清除，就必须去除中性粒细胞，以避免长时间的 以避免对周围组织造成伤害。细胞凋亡是中性粒细胞 功能性关闭、移走的中性粒细胞的清除以及炎症的及时解决。血小板是 无核血细胞在全身循环，在止血，伤口愈合， 血管生成、炎症和凝块形成。血小板自然充满分泌颗粒， 血小板活化后释放的大量生物活性蛋白质参与了多种 生理过程，包括调节炎症反应。该提案的目标是制定一个 模块化平台技术，利用合成生物学对多能干细胞进行重新编程， 用于治疗的工程血小板。为此，我们建议利用先天储存， 血小板的运输和释放能力，以构建可以调节和主动终止 中性粒细胞功能。

Project Summary Neutrophils are rapidly recruited to the sites of infection and injury to form the first line of defense against invading pathogens or tissue injury, and play a prominent role in the initiation and progression of the inflammatory response. However, once the pathogens are cleared, it is critical for neutrophils to be removed to avoid prolonged inflammation and to avoid inflicting damage to the surrounding tissue. Apoptosis is essential for neutrophil functional shutdown, removal of emigrated neutrophils, and the timely resolution of inflammation. Platelets are anucleate blood cells that circulate throughout the body and play an important role in hemostasis, wound healing, angiogenesis, inflammation, and clot formation. Platelets are naturally filled with secretory granules that store large amounts of bioactive proteins that are released following platelet activation to participate in a myriad of physiological processes, including modulating inflammatory responses. The goal of this proposal is to develop a modular platform technology using synthetic biology to reprogram pluripotent stem cells for the production of engineered platelets for therapeutic treatments. Towards this end, we propose to capitalize on the innate storage, trafficking, and release capabilities of platelets to build delivery vehicles that can modulate and actively terminate neutrophil function.