MSCs and EVs
DIABETES
KIDNEY INJURY
ALZHEIMER'S
DISEASE
ARDS
(LUNG INJURY)
INFLAMMATORY
BOWEL DISEASE
PANCREATIC
CANCER

KIDNEY INJURY

Acute Kidney Injury (AKI) occurs in a significant number of hospitalized patients, especially in those receiving chemotherapy or undergoing cardiovascular procedures.  While many patients recover, the kidneys are often left with residual damage which predisposes them to develop kidney dysfunction or chronic kidney disease in later life.  Our research focuses on stimulating a regenerative phenotype in the injured kidney as well as healing the kidney through locoregional delivery of MSC-based therapies.

Acute Kidney Injury

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Kidney diseases contribute a significant morbidity and mortality burden on society. Progression of acute kidney injury (AKI) and chronic kidney disease (CKD) can ultimately result in end stage renal disease, for which dialysis and kidney transplantation are the only treatment options. In recent years, there has been a substantial increase in hospitalizations for AKI. However, there is no approved therapy for stopping, or even reversing, kidney damage with the standard approach being mostly supportive in nature.

 

A promising approach to treat AKI is to administer mesenchymal stem cell (MSC)-based therapies directly into the kidney. We have shown that both parent MSCs (i.e. a cellular therapy) and MSC-derived extracellular vesicles (EVs; i.e. a cell-free therapy) can improve the survival and function of damaged kidneys. While MSCs can recover kidney function, reduce inflammation and increase cellular proliferation in animal models of AKI, MSC-derived EVs can decrease heat shock protein (HSP) 70, resulting in downregulation of the NLPRP3 inflammasome. In addition, we have developed techniques to deliver MSC-based therapies directly into

into the injured kidney in small animal models, by intra-arterial (IA) injection - similar to what can be achieved using endovascular approaches by interventional radiologists. This will avoid their first pass retention in the lungs and reticuloendothelial system following conventional intravenous infusion. Furthermore, we have shown that we can optimize the kidney microenvironment using a novel technology based on soundwaves called pulsed focused ultrasound (pFUS). Here, we observed that pFUS can upregulate HSP 20 and 40 in AKI, which results in activation of the P13K-AKT pathway; in turn, stimulating cellular proliferation while also decreasing apoptosis.