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

间充质干细胞衍生的 A-1 外泌体治疗创伤性脑损伤

• 批准号: 10186835
• 负责人: ASHOK K SHETTY
• 金额: $ 57.4万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10186835
• 关键词: Acute; Adverse effects; Alzheimer' s Disease; Animal Model; Anti-Inflammatory Agents; Behavior; Behavioral; Biological Assay; Brain; Caring; Cell Therapy; Cells; Chronic; Chronic Disease; Chronic Phase; Clinical; Cognitive; Disease; Disease model; Distress; Dose; Drug Kinetics; Healthcare Systems; Inflammation; Inflammatory Response; Injury; Intranasal Administration; Intravenous; Learning; Lipids; Location; Measures; Medical; Memory; Mesenchymal; Mesenchymal Stem Cells; Metabolic; Molecular; Moods; Mus; Natural Immunity; Parkinsonian Disorders; Patients; Pattern; Pharmaceutical Preparations; Phase; Problem behavior; Property; Proteomics; Protocols documentation; Publications; RNA; Reaction; Reagent; Reporting; Route; Safety; Short-Term Memory; Site; Societies; Standardization; Stress; Stromal Cells; Swimming; Syndrome; TBI treatment; Testing; Therapeutic Index; Traumatic Brain Injury; Travel; Vesicle; acquired immunity; adult stem cell; base; behavior test; behavioral impairment; cytokine; depressive symptoms; effective therapy; exosome; feeding; improved; mouse model; neuroinflammation; novel; novel therapeutics; object recognition; prevent; stem; water maze

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.

项目总结/摘要 间充质干细胞衍生的A1-外泌体用于创伤性脑损伤 该提案将为严重创伤性脑损伤（TBI）开发一种新的治疗方法， 对受害者产生毁灭性影响并造成巨大负担的状况。 美国医疗保健系统每年花费550亿美元。TBI的一个令人痛苦的特征是 在急性期之后，患者逐渐出现行为缺陷。作为 结果，这种疾病现在被认为是一种慢性综合征， 初始炎症反应过度的周期， 对大脑造成相当大的伤害，从而引发另一轮持久的 炎症已经测试了许多抗炎剂用于治疗TBI，但 尚未被接受为标准医疗护理的一部分。该提案基于 在早期的出版物中，证明了间充质干细胞/基质 细胞在TBI的动物模型中产生了有益的效果（通过MSC），主要是通过 减少炎症，以及我们和另一个实验室最近的观察， MSC的有益作用可以用产生的小囊泡（外来体）来再现， 的MSC。拟议的研究将确定以下药物的疗效、安全性和作用方式： TBI小鼠模型中的A1-外泌体。A1-外泌体由MSC制备， 可扩展的方案，其可用作“现成”试剂。我们将比较 静脉内或鼻内施用A1-外泌体，因为我们已经 最近发现，鼻内给予A1-外泌体显著降低了 诱发性神经炎症如果成功的话，这一提议将为一部小说提供基础。 临床治疗TBI和其他可能涉及神经炎症的疾病， 帕金森病和阿尔茨海默病。