Platelet-mitochondria transplantation to treat mitochondrial dysfunction in acute kidney injury

点击翻译按钮获取中文摘要

(PLEASE KEEP IN WORD, DO NOT PDF) This project responds directly to PAR-21-038; the PI changes direction from valvular heart disease to study acute kidney injury (AKI). Indeed, the PI is a new faculty member in the Division of Nephrology, Department of Medicine. The PI will apply her previous expertise in platelet structure to examine a new therapeutic approach to deliver mitochondria to injured kidneys and therefore stop the progression of AKI to end-stage renal disease. The PI is working closely with Dr. Daehn, an expert in kidney disease and mitochondrial function. In addition, she will be collaborating with Dr. Brestoff, an expert in mitochondria transplantation, to validate the proposed experimental approach. AKI is a critical health condition characterized by a sudden decline in kidney function. It occurs in approximately 20%-30% of hospitalized patients. In the US, AKI is leading to high morbidity and mortality. Although AKI encompasses various etiologies, tubular injury is an early and decisive step in AKI. During hypoxia, proximal tubular epithelial cells (PTECs) undergo oxidant stress, mitochondrial damage, protein synthesis inhibition, and growth arrest. Non-treated AKI can progress to chronic kidney disease (CKD) and end-stage renal disease. Renal replacement therapy is necessary for patients with a survival of only 10%. Currently, there are no pharmacological or preventive strategies available to reverse or reduce the occurrence of severe AKI or to stop its progression to chronic kidney disease and end-stage kidney, emphasizing the need for new therapeutic strategies in this area. The central hypothesis in this application will test an innovative approach to treating kidneys using mitochondria transplants to prevent AKI. This hypothesis will be tested in one Specific Aim; To examine a new delivery approach of competent mitochondria to isolated proximal tubular epithelial cells using naked mitochondria or encapsulated mitochondria.