Validation of a Stroke Therapy Comprised of Synergistic Stem Cell-Derived Factors

包含协同干细胞衍生因子的中风疗法的验证

• 批准号: 8980800
• 负责人: Brian H. Johnstone
• 金额: $ 20.33万
• 依托单位: THERATOME BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8980800
• 关键词: Acute; Adipose tissue; Adolescent; Adult; Alteplase; Animals; Biological; Blood flow; Bolus Infusion; Brain; Brain Injuries; Brain Ischemia; Cell Therapy; Cells; Cerebrovascular Disorders; Collaborations; Conditioned Culture Media; Data; Developed Countries; Development; Disease model; Dose; Drug Interactions; Effectiveness; Evaluation; FDA approved; Family suidae; Female; Fractionation; Goals; Harvest; Health Care Costs; Hospitals; Hour; Human; Image; In Vitro; Incidence; Individual; Injection of therapeutic agent; Intravenous; Ischemia; Ischemic Stroke; Laboratories; Lead; Legal patent; Magnetic Resonance Imaging; Medical; Mesenchymal Stem Cells; Modeling; Mus; Natural regeneration; Operative Surgical Procedures; Outcome; Patients; Penetration; Performance; Pharmaceutical Preparations; Phase; Population; Preparation; Process; Proteins; Qualifying; Research Infrastructure; Stem cells; Stroke; System; Temperature; Testing; Therapeutic; Time; Tissues; Toxic effect; United States; Validation; Western World; adult stem cell; aged; base; behavior test; cell motility; cerebral atrophy; clinically relevant; comparative efficacy; disability; drug candidate; functional improvement; functional outcomes; improved; in vivo; ischemic lesion; male; neurogenesis; novel; paracrine; public health relevance; repaired; research clinical testing; safety study; socioeconomics; stem cell therapy; stroke therapy; subventricular zone; thrombolysis; white matter; young adult

 DESCRIPTION (provided by applicant): Stroke is the leading cause of disability in adults in the Western world. Its socioeconomic impact is staggering. Most stroke patients currently have no treatment option given that the only FDA-approved stroke therapy, intravenous tPA for treatment of thrombolysis, must be administered within 5 hours of stroke onset and only about 5% of stroke patients present for treatment within that time window. The development of a therapy with a longer treatment window could benefit the other 95% of patients not currently served. Mesenchymal stem cell (MSC) therapies have shown promise in cerebrovascular disease models; however, their mechanism of action is predominantly through paracrine support of endogenous repair mechanisms rather than direct tissue replacement. We and others have demonstrated the therapeutic potential of cell-free conditioned medium derived from adult MSCs isolated from adipose tissues. Importantly, we have observed morphological and functional benefits when our therapy, NFx-101, is delivered up to 36 hours following onset of ischemia. We propose to demonstrate the efficacy of NFx-101, a partially purified adipose stem cell-derived conditioned medium, when delivered between 6 and 24 hours after ischemia in a clinically relevant, partially humanized mouse embolic stroke model. Mice will be evaluated for morphological and functional changes as a result of treatment. If successful, NFx-101 could become a breakthrough therapy for stroke victims.

 描述（由申请人提供）：中风是西方世界成年人残疾的主要原因。其社会经济影响是惊人的。大多数中风患者目前没有治疗选择，因为 FDA 批准的唯一中风疗法（用于溶栓治疗的静脉注射 tPA）必须在中风发作 5 小时内进行，并且只有约 5% 的中风患者在该时间窗口内接受治疗。开发一种治疗窗口更长的疗法可以使目前未接受治疗的其他 95% 的患者受益。间充质干细胞（MSC）疗法在脑血管疾病模型中显示出前景；然而，它们的作用机制主要是通过旁分泌支持内源性修复机制，而不是直接组织替代。我们和其他人已经证明了从脂肪组织中分离出的成体 MSC 衍生的无细胞条件培养基的治疗潜力。重要的是，我们观察到当我们的疗法 NFx-101 在缺血发作后 36 小时内给药时，在形态和功能上都有益处。我们打算证明 NFx-101（一种部分纯化的脂肪干细胞衍生的条件培养基）在临床相关的部分人源化小鼠栓塞性中风模型中缺血后 6 至 24 小时内递送时的功效。将评估小鼠因治疗而发生的形态和功能变化。如果成功，NFx-101可能成为中风患者的突破性疗法。