Abstract

BackgroundDiabetic nephropathy (DN) is considered as one of the most serious complications resulting from diabetes mellitus and end-stage of renal failure globally. Up to 40% of diabetic patients will develop DN. The involvement of mesenchymal stem cells (MSCs) in diabetic renal lesions management has been established in many animal models of DN. The aim is to evaluate the capability of MSCs and their culture medium (CM) to alleviate DN in streptozotocin (STZ)-induced diabetic rat model. Female albino rats were made diabetic and were further categorized into 4 subgroups of 15 each: DN group, DN group received fibroblasts, MSCs group received one dose of 1 × 106 cells of MSCs, and CM group received one dose of 500 μl of CM. In all groups, the treatment was delivered by intravenous injection (IV) into the tail vein.ResultsMSCs insinuated themselves into the injured kidney as detected by CD44 expression. Biochemical and histological results showed that MSCs and/or CM effectively attenuated DN manifestations in rat model through their possible anti-inflammatory (tumor necrosis factor-α and transforming growth factor-β1 were decreased), anti-apoptotic (Bcl2 was increased while Bax and caspases were decreased), and anti-oxidant role (malondialdehyde was decreased while glutathione and catalase were increased).ConclusionThese results provide a potential therapeutic tool for DN management through the administration of the CM from MSCs that ameliorates the effects of diabetes. It is also possible to treat DN using CM alone thus avoiding cell transplantation.

Highlights

  • Diabetic nephropathy (DN) is considered as one of the most serious complications resulting from diabetes mellitus and end-stage of renal failure globally

  • Characterization of Adipose tissue (AD)-mesenchymal stem cells (MSCs) Adipose-derived MSCs (AD-MSCs) were characterized by their adhesiveness and fusiform shape, spindle, and fibroblast-like cells

  • Sry gene (402 bp) was expressed in male rats from which AD-MSCs were isolated. It was detected in renal cells of female rats that were injected by malederived AD-MSCs in MSCs group

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Summary

Introduction

Diabetic nephropathy (DN) is considered as one of the most serious complications resulting from diabetes mellitus and end-stage of renal failure globally. The involvement of mesenchymal stem cells (MSCs) in diabetic renal lesions management has been established in many animal models of DN. The aim is to evaluate the capability of MSCs and their culture medium (CM) to alleviate DN in streptozotocin (STZ)-induced diabetic rat model. Diabetic nephropathy (DN) is the major micro-vascular complication in diabetic patients and accounts for approximately half of all end-stage renal disease globally [1]. The key characterized features of diabetic nephropathy include thickened basement membrane of both glomeruli and tubules, mesangial cell (MC) hypertrophy, extracellular matrix accumulation, tubule-interstitial fibrosis, and glomerular sclerosis which is the leading cause of micro-albuminuria and renal failure [2, 3]. Many factors have been proposed to be involved in the pathogenesis of diabetic nephropathies such as genetic and hemodynamic factors, metabolic, oxidative stress, and cytokine signaling [2, 4].

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