Therapeutic platform to treat disease lung using enucleated mesenchymal stem cells0/01/2021

迫切需要基于细胞的疗法，这种疗法可以静脉给药(IV)，并有效地在家中进行 向呼吸系统提供治疗药物，同时维护患者安全。Cytonus治疗公司和 加州大学圣地亚哥分校医学中心正在共同开发去核间充质干细胞，有可能提供 广泛的生物制剂用于治疗包括急性呼吸窘迫综合征(ARDS)在内的呼吸系统疾病。我们的 提供治疗的新平台是通过基因工程的方式将间充质干细胞 炎症归巢蛋白，然后轻轻移除细胞核，从而提供高度独特、可行和 安全细胞治疗(CargocytesTM)，具有显著的肺归巢潜力。摘除眼球使其能够 基因工程的Cargocell具有多个肺靶向部分和广泛的生物有效载荷， 同时保持临床相关的安全概况。我们的肺靶向战略建立在以下关键潜力之上 Cargocell疗法通过静脉途径(Iv)向肺部进行主动靶向递送。成核的 首先，骨髓间充质干细胞将被广泛地利用已建立的趋化受体CXCR4/CCR2和炎症 内皮细胞黏附分子PSGL-1，然后静脉注射前去核。行政管理。概念验证 然后将进行临床前研究，以确定碳细胞工程是否具有肺营养 在临床相关的急性呼吸窘迫综合征小鼠模型中，炎症肺部的分子。因此，目标1的研究将 确定使用CCXCR4/CCR2和PSGL-1工程的Cargocell是否为炎症肺组织和Aim 2的宿主 研究将确定碳细胞是否离开血管系统，进入炎症/受损的肺实质。如果 碳细胞聚集到炎症的肺组织并离开血管系统，它可以提供一种有效的手段来治疗 广泛的呼吸系统疾病。

There is critical need for cell-based therapeutics that can be administered intravenously (IV), and effectively home to and deliver therapeutics to the respiratory system, while maintaining patient safety. Cytonus Therapeutics and UC San Diego's Medical Center are co-developing enucleated mesenchymal stem cells with potential to deliver a wide range of biologics to treat respiratory diseases including acute respiratory distress syndrome (ARDS). Our novel platform for therapeutic delivery is to genetically engineer mesenchymal stem cells (MSCs) with inflammation homing proteins and then gently remove the nucleus, thereby providing a highly unique, viable, and safe cell therapeutic (CargocytesTM) with substantial lung homing potential. Enucleation grants the ability to genetically engineer Cargocytes with multiple lung targeting moieties and a wide range of biological payloads, while maintaining a clinically relevant safety profile. Our lung targeting strategy is built on the key potential of Cargocyte therapeutics to perform active-targeted delivery to the lungs via an intravenous route (i.v.). Nucleated MSCs will first be extensively engineered with established chemoattractant receptors CXCR4/CCR2 and inflamed endothelial adhesion molecule PSGL-1 and then enucleated prior to i.v. administration. Proof-of-concept preclinical studies will then be performed to determine whether Cargocytes engineered with lung trophic molecules home to inflamed lungs in a clinically relevant murine model of ARDS. Therefore, Aim 1 studies will determine if Cargocytes engineered with CCXCR4/CCR2 and PSGL-1 home to inflamed lung tissues and Aim 2 studies will determine if Cargocytes exit the vasculature and move into the inflamed/damaged lung parenchyma. If Cargocytes home to inflamed lung tissues and exit the vasculature, it could provide an effective means to treat a wide range of respiratory diseases.