Transforming Dialysis into a Controlled Drug Delivery System for Stem Cell Derive

描述（由申请人提供）：该IIB期SBIR申请的目标是在首次人体研究中测试Sentien细胞生物反应器产品（Sentinel），以评估安全性和初步疗效。15名诊断为急性肾损伤并需要透析的心脏手术后患者将被纳入并连接到Sentinel， Sentinel含有三种递增剂量的细胞，每剂量n=5: 250M、500M和1000M。主要终点涉及安全性措施，患者样本将由Sentien进行分析，以评估可能的疗效趋势。该项目的具体目标是：(1)对诊断为AKI并指征为CVVH的心脏手术患者进行单中心、开放标签、剂量递增的Sentinel安全性研究；(2)测量实验性尿液生物标志物，初步监测设备的有效性；(3)分析患者血液配对检测中的炎症反应途径。该项目的可交付成果应为：(1)与历史对照相比，Sentinel的不良事件记录；(2)通过尿液生物标志物、血清细胞因子和体外血液单个核细胞测定来测量初步疗效数据。

DESCRIPTION (provided by applicant): The goal of this Phase IIB SBIR application is to test the Sentien cellular bioreactor product (the Sentinel") in a first-in-man study to assess safety and preliminary efficacy. Fifteen post-cardiac surgery patients that are diagnosed with acute kidney injury and indicated for dialysis will be enrolled and connected to the Sentinel containing one of three escalating doses of cells, n=5 per dose: 250M, 500M and 1000M. Primary endpoints involve measures of safety, and patient samples will be taken for analysis by Sentien to evaluate possible trends in efficacy. The project specific aims are: (1) conduct a single- center, open-label, dose escalation safety study of the Sentinel in cardiac surgery patients diagnosed with AKI and indicated for CVVH; (2) measure experimental urine biomarkers for preliminary monitoring of device efficacy; and (3) profile the inflammatory response pathway in paired testing of patient blood. The deliverables of this project will be (1) a record of adverse events with the Sentinel compared to historical controls; and (2) preliminary efficacy data as measured by urine biomarkers, serum cytokines and ex vivo blood mononuclear cell assays.