gms | German Medical Science

Introduction: Cell-based therapies were reported to improve early kidney function in experimental models of renal ischemia-reperfusion injury. This study examines and compares the therapeutic effects of mesenchymal stem cells (MSC) and endothelial progenitor cells (EPC) as well as their regenerative capacity in the long-term.

Materials and methods: The effects of cellular therapy using MSC and EPC were investigated following a 45 min warm ischemia in a murine model of renal ischemia-reperfusion injury. Renal function was measured by ^99mTc-MAG3 scintigraphy and laser Doppler perfusion in the acute phase (day 2) and in the long-term (day 18). Structural damage was assessed by histological analysis.

Results: Without therapy, warm ischemia of 45 min led to a significant decrease in tubular function (day 2: 31.4% ± 7.7%, p<0.01; day 18: 46.4% ± 12.5%, p<0.01) and renal perfusion (67.7% ± 3.9%, p<0.01) as well as severe tissue damage 18 days post ischemia. In ischemic kidneys renal blood flow was completely restored by day 18 using EPC (112.5% ± 3.1%, p<0.001), but only moderately using MSC (80.6% ± 2.6%, p<0.05). Renal function remained impaired for both EPC and MSC. Histologically, both cell-based treatment options showed reduced structural damage. EPC-treated kidneys exhibited no necrosis, but increased inflammatory infiltration. In contrast, MSC therapy led to reduced postischemic inflammation and improved preservation of renal structures.

Conclusion: Cell-based therapies using EPC/ MSC for renal ischemia-reperfusion injury exert differential effects in the long-term. EPC treatment improves kidney perfusion, in particular. In contrast, MSC show beneficial effects in terms of reduced postischemic inflammation that may be attributed to their immunomodulatory properties. These positive effects provide potent add-ons to already established therapeutic strategies such as surgical decompression using microcapsulotomy.