Transplantation of Allogenic Fetal Membrane-Derived Mesenchymal Stem Cells Protects against Ischemia/Reperfusion-Induced Acute Kidney Injury

Abstract

Mesenchymal stem cells (MSCs) are an attractive therapeutic cell source for treating renal diseases. MSC administration has been shown to improve renal function, although the underlying mechanisms are not completely understood. We recently showed that allogenic fetal membrane-derived MSCs (FM-MSCs), which are available noninvasively in large amounts, had a renoprotective effect in an experimental glomerulonephritis model. Here we investigated whether allogenic FM-MSC administration could protect kidneys from ischemia/ reperfusion (I/R) injury. Lewis rats were subjected to right nephrectomy and left renal I/R injury by clamping the left renal artery as an acute kidney injury (AKI) model. After declamping, FM-MSCs (5 × 105 cells) obtained from major histocompatibility complex (MHC)-mismatched ACI rats were intravenously administered. I/R-injured rats exhibited increased serum creatinine and BUN, whereas FM-MSC administration significantly ameliorated renal function. Histological analysis revealed that FM-MSC administration significantly suppressed tubular apoptosis and infiltration of macrophages and T-cells. Administration of FM-MSCs mainly homed into the lung, but increased serum IL-10 levels. Of interest is that renoprotective effects of FM-MSCs were abolished by using anti-IL-10 neutralization antibody, suggesting that IL-10 would be one of the candidate factors to protect rat kidney from I/R injury in this model. We concluded that allogenic FM-MSC transplantation is a potent therapeutic strategy for the treatment of AKI.