MSCs for renal repair

Abstract

Acute kidney injury (AKI), the abrupt loss of renal function that results from ischemia, sepsis, or nephrotoxin-induced damage to vascular and tubular structures, is characterized by inflammatory processes, cellular apoptosis, and necrosis. Patient mortality remains high and treatment is largely supportive. Even mild AKI can lead to chronic kidney disease (CKD), further underscoring the urgent need for therapeutic innovations. Mesenchymal stromal cells' (MSCs) potent antiinflammatory, immunomodulatory, organ protective, and reparative properties make them excellent potential candidates for prevention and treatment of AKI. Multiple preclinical studies using various AKI models have confirmed that, via paracrine mechanisms, MSC treatment improves survival, ameliorates and reverses injury, and prevents progression to CKD. Preliminary results from the first Phase I clinical trial (safety, preliminary efficacy), in which we infused allogeneic MSCs into subjects at high risk for AKI following on-pump cardiac surgery, paralleled preclinical observations, suggesting that MSC therapy is safe and effective in preventing both postoperative AKI and progression to CKD.