Principal Investigator: John D. Jackson, PhD; Co-PI Ji Hyun Kim, PhD
Organization: Wake Forest Institute for Regenerative Medicine
Acute kidney injury (AKI) is seen at a significantly high incidence in critically injured patients and is associated with increased mortality. In Iraq and Afghanistan wars, for instance, the rate of AKI in soldiers treated in the intensive care unit due to amputation, burn injury, and gunshot wounds were 34.3%, with a mortality rate of 21.7%. Renal replacement therapy and cell-based treatment are used to treat AKI; however, these methods can be challenging in combat situations. Since the treatment effects of cell therapies are believed to result from the secreted bioactive molecules produced by the infused cells, treatments using stem cell-derived conditioned medium (CM) (referred to as secretome) have emerged as a promising option for kidney disease. However, safety and regulatory concerns exist due to the uncharacterized biochemical contents and variability across different batches of CM samples. To address these concerns, we propose a standardized, off-the-shelf, and clinically feasible treatment using fully characterized recombinant proteins identified by the CM analysis for immediate care of kidney disease. Lyophilized recombinant proteins remain stable when stored at ambient temperatures; therefore, they can be used for immediate care of AKI in a forward hospital setting. The objective of this project is to develop stem cell secretome-based recombinant proteins to prevent the progression of renal damage and facilitate rapid recovery of renal function closer to the point of need. In this project, we will 1) Refine and validate the recombinant protein delivery in vitro; 2) Evaluate the clinical feasibility of restoring renal function in a large animal AKI model; 3) Develop standard operating procedures (SOPs) and regulatory strategy.