Effect of Mesenchymal Stem Cells Therapy on Cardiovascular Risk in Experimental Diabetic Kidney Disease

Abstract

Abstract Background Bone Marrow-derived Mesenchymal stem cells (MSC)s were experimentally used in treating diabetes mellitus (DM) and its complications, particularly, diabetic kidney disease (DKD). Cardiovascular diseases are the leading cause of mortality in diabetic patients, which has been strongly associated with progression of DKD. Aim This study was designed to explore the effect of MSCs in modulating cardiovascular risk factors that develop with DKD. Study Design 60 adult female albino rats were allocated into three groups: control group, untreated diabetic kidney disease group (un-DKD) and MSCs treated diabetic kidney disease group (MSC-DKD). DM was induced by a single dose of Streptozotocin at a dose of 35mg/kg, then rats were sacrificed 8 weeks later. MSC-DKD rats were treated by IV injection of bone marrow-derived MSCs 4 weeks after DM induction. DKD establishment was confirmed by histopathological kidney changes and elevated plasma creatinine and urea in both un-DKD and MSC-DKD rats. Methods Blood Pressure and lipid profile were measured, and atherogenic index was calculated to assess cardiovascular risk accompanying the progression of the diabetic renal damage. Moreover, aortic reactivity studies were performed in vitro. Results A single MSCs injection to MSC-DKD rats resulted in significant decrease in final blood glucose, mean arterial blood pressure and atherogenic index, together with a significant increase in plasma HDL level compared to untreated rats, thus minimizing cardiovascular risk factors. MSC-DKD aortae also exhibited significant enhancement of vascular reactivity parameters, particularly vasorelaxation which could partially explain the improvement of blood pressure. On the other hand, DKD didn’t improve by MSCs therapy. These results conformed to tracking labelled MSCs which were found in abundance in both aortic and pancreatic tissues and absent in kidneys. Conclusion MSCs therapy holds hope of improving cardiovascular risk and mortality for diabetic patients with diabetic Kidney disease.