Protective Effect of Wharton's Jelly-derived Mesenchymal Stem Cells on Renal Fibrosis in Rats with Unilateral Ureteral Obstruction

Abstract

Background Renal failure is a global medical problem. The use of mesenchymal stem cells (MSCs) for preservation and regeneration of renal tissue in acute and chronic kidney diseases has recently been the focus of investigation. Objective To evaluate the protective effect of MSC injections in a rat model of kidney obstruction. Design, setting, and participants We assigned 15 male Wistar rats to three separate groups: the normal group underwent left nephrectomy; the control group underwent laparotomy and left ureter ligation followed by saline injection into the aorta; and the study group received MSCs injected into the aorta inferior to the left renal artery after ligation of the left ureter. Kidneys were harvested 4 wk later and renal parenchyma samples were used for trichrome staining and for expression analyses. Outcome measurements and statistical analysis The degree of kidney fibrosis was assessed on pathology. Real-time polymerase chain reaction was used to determine expression levels of VEGF, TNF-α, and E-cadherin, and ΔCT and ΔΔCT values were calculated. Data were analyzed using SPSS v19 with paired t tests and nonparametric independent-sample Kruskal-Wallis tests. Results and limitations Fibrosis in the study group decreased from grade 3 or 4 to grade 1. In the control group, TNF-α expression increased and E-cadherin expression decreased. After MSC injection into obstructed kidneys, TNF-α and E-cadherin expression levels decreased and increased respectively, reaching similar levels to those in the normal group. No correlation between tissue regeneration and VEGF levels was observed. More research is needed to focus on other angiogenic factors. Conclusions MSC injection could prevent fibrosis in obstructed rat kidney via alterations in TNF-α and E-cadherin expression. Patient summary We investigated the effect of stem cell injection in rats with kidney obstruction. The treatment led to changes in the levels of two biomarkers and reduced the amount of kidney fibrosis caused by kidney obstruction.

Possible Underlying Mechanisms for the Renoprotective Effect of Retinoic Acid-Pretreated Wharton’s Jelly Mesenchymal Stem Cells against Renal Ischemia/Reperfusion Injury

“…Furthermore, we reported significant improvement in renal function parameters, including serum creatinine, BUN, urinary proteins, and kidney morphology in the WJ-MSCs group, suggesting and confirming the renoprotective effect of the WJ-MSCs on renal IRI injury. These findings agreed with previous experimental studies that demonstrated the effectiveness of using stem cell therapy against renal IRI injury [9,[29][30][31].…”

Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets

“…Umbilical cord-derived MSC, specifically the stem cells harvested from Wharton's Jelly, demonstrate promise for future clinical applications because of their limited heterogeneity and easy accessibility in numerous tissues [291,292]. Compared to bone marrow-derived MSC, umbilical cord-derived MSC have lower immunogenicity and superior ability to proliferate and differentiate, and they can be isolated without any invasive surgical procedure and manufactured in large quantities without compromising potency [289,293,294].…”