Mesenchymal Stem Cell Derived A-1 Exosomes for Traumatic Brain Injury

项目摘要/摘要 “骨髓间充质干细胞衍生的A1-exosome治疗创伤性脑损伤” 这项提议将开发一种治疗重型创伤性脑损伤的新方法，即 对受害者造成毁灭性影响并造成巨大负担的状况 每年在美国医疗体系上的支出为550亿美元。TBI的一个令人苦恼的特征 就是急性期过后，患者逐渐出现行为缺陷。作为一名 结果，该病现在被认为是一种慢性综合征，涉及粘液 初始炎症反应过度的循环，从而导致 对大脑造成相当大的损伤，从而引发另一轮持久的 发炎。许多抗炎药已经被测试用于治疗脑损伤，但 目前还没有一个被接受为标准医疗保健的一部分。这项建议是基于 关于早期关于间充质干细胞/基质给药的文献 细胞在脑外伤动物模型中产生了有益的影响(通过间充质干细胞)，主要是通过 减少炎症，我们和另一个实验室最近的观察表明 骨髓间充质干细胞的有益效果可以通过产生小囊泡(外体)来复制。 被骨髓间充质干细胞。拟议的研究将确定该药的有效性、安全性和作用方式。 脑外伤小鼠模型中的A1-exosome。A1-exosome是从具有 可扩展的协议，可用作“现成”试剂。我们将比较 静脉或鼻腔给药A1-exosome，因为我们已经 最近发现，鼻腔内给药的A1-exosome显著减少 诱发性神经炎。如果成功，这项提议将为一部小说提供基础 脑损伤的临床治疗，可能还有其他涉及神经炎症的疾病，如 帕金森氏症和阿尔茨海默氏症。

Project Summary/Abstract “Mesenchymal Stem Cell Derived A1-Exosomes for Traumatic Brain Injury” This proposal will develop a novel therapy for severe traumatic brain injury (TBI), a condition that has devastating effects on the victims and creates a large burden over $55 billion per year on the US healthcare system. One of the distressing features of TBI is that after the acute phase, the patients gradually develop behavioral deficits. As a result, the disease is now considered as a chronic syndrome that involves a viscous cycle in which the initial inflammatory response is excessive so that it causes considerable injury to the brain and thereby triggers another round of lasting inflammation. Numerous anti-inflammatory agents have been tested for treating TBI, but none have yet been accepted as part of standard medical care. This proposal is based on earlier publications that demonstrated administration of mesenchymal stem/stromal cells produced beneficial effects in animal models of TBI (by MSCs), primarily through reducing inflammation, and the more recent observation by us and another lab that the beneficial effects of MSCs can be reproduced with small vesicles (exosomes) produced by MSCs. The proposed studies will establish the efficacy, safety, and mode of action of A1-exosomes in a mouse model of TBI. A1-exosomes are prepared from MSCs with a scalable protocol, which can be used as “off-the-shelf” reagents. We will compare the administration of A1-exosomes either intravenously or intranasally since we have recently found that intranasal administration of A1-exosomes dramatically reduces induced-neuroinflammation. If successful, the proposal will provide the basis for a novel clinical therapy for TBI and perhaps other diseases involving neuroinflammation such as Parkinsonism and Alzheimer’s disease.