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Abstract

Objectives: Mesenchymal stem cells hold promise for renal disease treatment. Vascular endothelial growth factor may heal tubule-interstitial fibrosis in unilateral ureteral obstruction by inhibiting epithelial-mesenchymal transition. We investigated the protective effect of vascular endothelial growth factor in transfected mesenchymal stem cells in unilateral ureteral obstruction-induced renal injury in rats. Materials and Methods: Male Wistar Albino rats (32 rats; weight, 250-300 g) were divided into 4 equal groups: group 1, control; group 2, unilateral ureteral obstruction; group 3, unilateral ureteral obstruction and mesenchymal stem cells; and group 4, unilateral ureteral obstruction and vascular endothelial growth factor-transfected mesenchymal stem cells. Vascular endothelial growth factor-transfected mesenchymal stem cells were administered intravenously before onset of unilateral ureteral obstruction. On day 14, the rats were killed and kidneys were retrieved. Tubular necrosis, mono-nuclear cell infiltration, and interstitial fibrosis were evaluated in paraffin blocks. We evaluated green fluorescent proteinpositive and vascular endothelial growth factorpositive cells; anti-inflammatory (Prostaglandin E2 Receptor) and interleukin 1 receptor antagonist), proinflammatory/anti-inflammatory (interleukin 6), and proinflammatory (MPO) cytokine expression levels; and levels of nitric oxide; transforming growth factor β1, E-cadherin, and hydroxyproline. Results: Green fluorescent protein-positive cells were negative in the renal parenchyma in groups 1 and 2 and positive in groups 3 and 4. Vascular endothelial growth factor levels were significantly higher in group 4. Transforming growth factor β1, nitric oxide, and E-cadherin levels were significantly higher in the unilateral ureteral obstruction than control group; however, in the study groups, these values were not significantly different from the unilateral ureteral obstruction group. In stem celltransplanted tissue samples, EP3, interleukin 1 receptor antagonist, and interleukin 6 levels were elevated, but MPO expression levels were low. Although there were significant differences for tubular necrosis and fibrosis in group 2, there were significant reductions in tubular injury and fibrosis in groups 3 and 4. Conclusions: Systemic stem cells transplanted into the kidney protected against unilateral ureteral obstruction-induced renal epithelial-mesenchymal transition and renal fibrosis.

miR-377 Inhibits Proliferation and Differentiation of Bovine Skeletal Muscle Satellite Cells by Targeting FHL2

“…SMSCs remain resting in unstressed, mature muscle, until the muscle is damaged or stimulated, at which time they become synchronously activated to provide new myo-nuclei for the myofiber [ 33 ]. Mesenchymal stem cells also contribute to maintaining the integrity of muscle structure and function [ 34 ]. The growth rate of muscles during postpartum development is particularly important in animal meat due to their high economic value.…”

Precision gene editing technology and applications in nephrology

“…Over time, studies examining the effects of exogenous gene expression have evolved to include modifiers of endogenous gene expression such as DNA enzymes 143 , decoy oligonucleotides 144,145 , siRNA 146,147 , and antisense oligonucleotides (Table 2) 148,149 . Additionally, multiple delivery methods have been explored including hydrodynamic injection into the tail vein 145,150 , renal electroporation 143,151 ultrasound with microbubbles 152-154 and expression of transgenes within mesenchymal stem cells 155 . Delivery by injection directly to the kidney has shown benefits in models of diabetic nephropathy, ischemia/reperfusion injury, tubulointerstitial and glomerular fibrosis 144,155-158 .…”

“…Additionally, multiple delivery methods have been explored including hydrodynamic injection into the tail vein 145,150 , renal electroporation 143,151 ultrasound with microbubbles 152-154 and expression of transgenes within mesenchymal stem cells 155 . Delivery by injection directly to the kidney has shown benefits in models of diabetic nephropathy, ischemia/reperfusion injury, tubulointerstitial and glomerular fibrosis 144,155-158 . These genome engineering systems and cellular delivery knowledge are being deployed anew with gene editing tools as cargo.…”

Current Perspectives on Role of MSC in Renal Pathophysiology

“…Most of the repair is the result of the fusion of bone marrow-derived and tubular cells, rather than direct trans-differentiation, even when the fusion involves hematopoietic-derived myelomonocytic cells instead of MSCs. Another strong evidence is a study by Ozbek et al (2015) on the protective effect of the vascular endothelial growth factor (VEGF) and MSC transplantation on renal injury induced by UUO. Stem cells transplanted into the kidneys prevented RF while preventing UUO from causing epithelial–mesenchymal transitions (EMTs).…”