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

Alireza Kheradmand; Mahmood Hashemitabar; Parvin Kheradmand; Farzin Valizadeh; Aryan Kavosh

doi:10.1016/j.euros.2020.06.004

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

Eur Urol Open Sci. 2020 Aug 17:20:48-53. doi: 10.1016/j.euros.2020.06.004. eCollection 2020 Jul.

Authors

Alireza Kheradmand¹, Mahmood Hashemitabar², Parvin Kheradmand³, Farzin Valizadeh¹, Aryan Kavosh⁴

Affiliations

¹ Urology Department, Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
² Anatomy and Embryology Department, Ahwaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
³ Pathology Department, Imam Khomaini Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
⁴ Isfahan University of Medical Sciences, Isfahan, Iran.

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.

Keywords: Kidney failure; Mesenchymal stem cells; Renal fibrosis; Renal obstruction.