Prophylaxis against renal ischemia-reperfusion injury in canine model: Stem cell approach

Abstract

Introduction: Stem cell therapy at the time of ischemia/reperfusion (I/R) injury has been hypothesized to attenuate the severity of acute kidney injury and to accelerate the regeneration process in lower animal models. Data in higher animal models is limited and discordant. We aimed to explore the reno-protective effects of stem cells on I/R related renal injury in a canine model. Materials and Methods: Twenty-seven dogs that were treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) were compared with another 27 dogs treated with adipose tissue-derived MSCs (AT-MSCs) following 90 min of warm ischemia to assess IR injury. Each group was divided into three subgroups (nine dogs each), according to the stem cell dose (5, 10, 15 × 106 in 500 μl volume) injected directly into the renal cortex after reperfusion. All dogs were re-evaluated by renogram, histopathology, and pro-inflammatory markers at 2 weeks, 2, and 3 months. Results: In Group I, there was a mean reduction of creatinine clearance by 78%, 64%, and 74% at the three used doses, respectively, at 2 weeks. At 3 months, these kidneys regained a mean of 84%, 92%, and 72%, respectively, of its basal function. In Group II, the reduction of clearance was much more modest with mean of 14%, 6%, and 24% respectively at 2 weeks with more intense recovery of renal function by mean of 90%, 100%, and 76%, respectively, at 3 months. Group I had significantly more tubular necrosis and delayed regeneration compared with the Group II. Expressions of pro-inflammatory markers were upregulated in both the groups with a higher and more sustained expression in Group I. Conclusion: Stem cells protected against ischemic reperfusion injury in a canine model. AT-MSCs provided better protection than BM-MSCs.