Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair

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Chronic kidney diseases (CKD) affect millions of people in the world and they represent an important public health problem,1 owing to the increasing incidence as well as prevalence and the high costs of treatment. The latest estimates of the World Health Organization suggested a CKD prevalence of over 10%, including end stage renal disease (ESRD).2 Many therapies have been developed in an attempt to reduce damage progression in CKD. The major impact on reducing the risk of developing ESRD has been achieved by renin angiotensin aldosterone system blockers.3 The renin‐angiotensin system (RAS) has been shown to influence cell proliferation and sclerosis as well as to regulate glomerular hemodynamics. Angiotensin II upregulates the immunoexpression of transforming growth factor‐β (TGF‐β) and the administration of angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) decreases the progression of glomerular sclerosis and interstitial fibrosis in experimental models of several nephropathies including cyclosporine (CsA) nephrotoxicity.4
Although administration of these drugs reduces proteinuria, they have not shown significant improvement in the glomerular filtration rate (GFR) or tubular function; moreover, the chronic administration of these drugs increases the risk of hyperkalemia.5 These facts have fuelled the search for new therapeutic strategies that could help in achieving better results. Mesenchymal stem cells (MSCs) are proved to be involved in the regeneration of many tissues subjected to different types of injury.6 Since, AD‐MSCs are a new alternative that have recently been evaluated in a chronic renal damage model with promising results. This source of MSCs was also used to treat the nephrotoxic effects of CsA in this study.
Cyclosporine is an immunosuppressive drug that has been used after solid organ transplantation to prevent allograft rejection and for the treatment of various autoimmune diseases. Long‐term treatment with this drug has been limited due to the concomitant development of chronic nephrotoxicity.7
Cystatin C (CYS‐C) is a cysteine protease inhibitor with a molecular weight of 13 kDa and is produced by nearly all nucleated cells.8 After entering the blood stream, serum cystatin C (S‐CYS‐C) is freely filtered by the glomeruli and subsequently reabsorbed and degraded by proximal epithelial tubular cells. Therefore, its serum concentration depends on the glomerular filtration rate and thus it is thought to be a more reliable indicator for the reduction of GFR than of serum creatinine.9
N‐Acetyl‐β‐glucosaminidase (NAG), a urinary enzyme, has been proposed as a valuable marker for kidney dysfunction. It is a lysosomal enzyme of 130 kDa molecular mass, normally excreted in low amounts in urine as a consequence of the normal exocytosis process.10
This study was planned to explore the therapeutic efficacy of bone marrow derived mesenchymal stem cells and adipose tissue derived mesenchymal stem cells in restrained nephropathy induced by CsA in a rat model. In addition, the study was extended to elucidate the role of stem cell versus angiotensin converting enzyme inhibitor in kidney repair.
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