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

描述（由申请人提供）：本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。将入组15名诊断为急性肾损伤并适合透析的心脏手术后患者，并将其连接至含有三种递增剂量细胞之一的Sentinel，每种剂量n=5：250 M、500 M和1000 M。主要终点涉及安全性指标，Sentien将采集患者样本进行分析，以评价疗效的可能趋势。该项目的具体目标是：（1）在诊断为阿基并适用于CVVH的心脏手术患者中进行Sentinel的单中心、开放标签、剂量递增安全性研究;（2）测量实验性尿液生物标志物以初步监测器械有效性;（3）在患者血液配对检测中分析炎症反应途径。本项目的可交付成果将是（1）与历史对照相比，Sentinel的不良事件记录;和（2）通过尿液生物标志物、血清细胞因子和离体血液单核细胞测定测量的初步疗效数据。

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.