Comparison of the effects of mesenchymal stem cell and exosome administration on kidney damage in rats using an intestinal ischemia-reperfusion model

General Surgery, Medical Specialty Thesis, Eskişehir, 2025. Intestinal ischemia reperfusion (IIR) injury is not limited to the intestine but initiates a systemic inflammatory response that causes distant organ injury, with the kidneys being highly susceptible due to their intense metabolic activity and intricate microvasculature. In the literature, stem cell and exosome therapies have been reported to exert anti-inflammatory and antifibrotic effects in IIR-related distant organ damage, except in the kidneys. Therefore, this study comparatively evaluated the therapeutic potential of human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSCs) and their exosomes in renal injury following IIR. In the experimental model, 32 male Wistar Albino rats were assigned to four groups. In Group I (sham), laparotomy and superior mesenteric artery (SMA) manipulation were performed before closure. In the other groups, the SMA was clamped for 45 minutes followed by reperfusion. In Group III (IIR+hWJ-MSC) and Group IV (IIR+hWJ-MSC Exosome), intraperitoneal MSCs or exosomes were given at the onset of reperfusion. All rats were sacrificed after 48 hours, and blood and kidney tissue samples were obtained. Serum creatinine and blood urea nitrogen (BUN) were measured. Renal tissue was examined histologically by light microscopy. Tissue levels of TGF-β1, IL18 and KIM-1 were evaluated by ELISA, while HIF-1α, CD68 and MCP-1 expressions were assessed by PCR. The results showed significant improvement in both treatment groups, with decreases in creatinine, BUN, TGF-β1, IL-18, KIM-1, HIF-1α, CD68 and MCP-1 levels, along with better histopathological outcomes. However, no significant superiority was detected between hWJ-MSCs and hWJMSC-derived exosomes. Overall, these findings indicate that both hWJ-MSCs and their exosomes are promising preventive strategies for reducing renal injury after IIR. Still, additional preclinical and large scale studies are required to confirm these results and strengthen their translational relevance. Key Words: Ischemia-reperfusion, mesenchymal stem cell, exosome. Supported By: ESOGU Scientific Research Projects Coordination Unit