Abstract:
Introduction: Diabetic nephropathy (DN) is one of the most prevalent microvascular consequences of diabetes that results in end-stage renal disease. Bone marrow - mesenchymal stem cells (BM-MSCs) and their secreted extracellular vesicles (EVs) become prospective treatment approaches for DN.
Aim: To compare the therapeutic potential of BM-MSCs and EVs on induced diabetic nephropathy in rats.
Materials and Methods: Four young male albino rats were utilized for isolation of BM-MSCs and EVs. Forty-two adult male albino rats were divided as follow: Group I (Control group): 18 rats. Group II (treated group): 24 rats, each administered an intraperitoneal streptozotocin injection (STZ) once (55 mg/kg body weight). After proved being diabetic (blood glucose > 250 mg/dl), they were further subdivided equally into: subgroup IIA (DN subgroup), subgroup IIB (spontaneous recovery subgroup), subgroup IIC (DN + BM-MSCs) and subgroup IID (DN + EVs). At the end of the research, blood and urine samples were taken for biochemical evaluation. For light, electron, and histo-morphometric investigations, the kidneys were removed and processed. The collected data underwent statistical analysis.
Results: Histological examination of DN subgroup revealed irregular thickened glomerular basement membrane (GBM), detached apoptotic endothelial cells, vacuolated parietal cells, effacement of the secondary processes of podocytes, inflammatory cells infiltration, mesangial cell proliferation and mesangial matrix expansion. These findings were confirmed biochemically by significant increase of kidney parameters, oxidative and inflammatory markers with significant decrease of antioxidant markers. Morphometric studies showed significant increase of GBM thickness and area percentage of collagen fibers. Treatment with BM-MSCs alleviated renal corpuscles histological changes and improved biochemical markers and morphometric analysis induced by diabetes. The administration of EVs revealed better results.
Conclusion: MSCs and EVs could be quite beneficial for treating DN. However, EVs have promising therapeutic modality over transplanted BM-MSCs with fewer side effects.