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

 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。它的社会经济影响是惊人的。大多数卒中患者目前没有治疗选择，因为FDA批准的唯一卒中治疗（用于溶栓治疗的静脉内tPA）必须在卒中发作后5小时内给药，只有约5%的卒中患者在该时间窗内接受治疗。开发具有更长治疗窗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，其作用机制主要是通过内源性修复机制的旁分泌支持，而不是直接的组织替代。我们和其他人已经证明了从脂肪组织分离的成人MSC衍生的无细胞条件培养基的治疗潜力。重要的是，我们已经观察到形态和功能的好处时，我们的治疗，NFx-101，提供长达36小时后缺血发作。我们建议在临床相关的部分人源化小鼠栓塞性中风模型中，在缺血后6至24小时之间递送NFx-101（一种部分纯化的脂肪干细胞衍生的条件培养基）时，证明其功效。将评价小鼠因给药引起的形态学和功能变化。如果成功，NFx-101可能成为中风患者的突破性疗法。

 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.