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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目概要/摘要 “间充质干细胞衍生的 A1-外泌体治疗创伤性脑损伤” 该提案将开发一种治疗严重创伤性脑损伤（TBI）的新疗法，一种对受害者造成毁灭性影响并造成巨大负担的情况美国医疗保健系统每年损失 550 亿美元，这是 TBI 的一个令人痛苦的特点。急性期过后，患者逐渐出现行为缺陷。结果，这种疾病现在被认为是一种慢性综合征，涉及粘性初始炎症反应过度从而导致的循环对大脑造成相当大的伤害，从而引发另一轮持久的许多抗炎药物已被测试用于治疗 TBI，但是尚未被接受为标准医疗护理的一部分。关于证明间充质干/基质管理的早期出版物细胞在 TBI 动物模型（通过 MSC）中产生有益作用，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结果 MSC 的有益作用可以通过产生的小囊泡（外泌体）来重现拟议的研究将确定 MSC 的功效、安全性和作用方式。 TBI 小鼠模型中的 A1-外泌体是用 MSC 制备的。可扩展的协议，可以用作“现成的”试剂，我们将比较这些协议。静脉内或鼻内给予 A1-外泌体，因为我们有最近发现，鼻内施用 A1-外泌体可显着降低如果成功，该提案将为小说提供基础。 TBI 以及其他涉及神经炎症的疾病的临床治疗，例如帕金森症和阿尔茨海默病。