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.
Sentien Biotechnologies Inc. has developed a patented bioreactor system (called the Sentinel) for harvesting the diverse array of therapeutic molecules secreted by mesenchymal stem cells (MSCs) and delivering them to a patient via the current dialysis infrastructure. In this proposal, we seek to conduct our first-in-man study of the Sentine in the target population for the lead indication, acute kidney injury (AKI). AKI is an insidious syndrome with an unacceptably high mortality. Previous attempts to treat AKI have sought to address single aspects of the pathophysiology, whereas the Sentinel delivers the diverse mixture of factors naturally secreted by MSCs, including molecules that can calm the immune system, protect injured tissue and boost natural repair mechanisms. The Sentinel is poised to revolutionize acute care by being the first multi-factorial therapy for complex diseases. With the completion of the studies proposed, Sentien will be prepared to advance this technology through remaining clinical studies and rapidly address this critical unmet need.