Amniotic Fluid Derived Stem Cells with a Renal Progenitor Phenotype Inhibit Interstitial Fibrosis in Renal Ischemia and Reperfusion Injury in Rats

Abstract

ObjectivesMesenchymal stem cells derived from human amniotic fluid (hAFSCs) are a promising source for cellular therapy, especially for renal disorders, as a subpopulation is derived from the fetal urinary tract. The purpose of this study was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a nephroprotective effect in acute ischemia reperfusion (I/R) model and prevent late stage fibrosis.MethodsA total of 45 male 12-wk-old Wistar rats were divided into three equal groups;: rats subjected to I/R injury and treated with Chang Medium, rats subjected to I/R injury and treated with hAFSCs and sham-operated animals. In the first part of this study, hAFSCs that highly expressed CD24, CD117, SIX2 and PAX2 were isolated and characterized. In the second part, renal I/R injury was induced in male rats and cellular treatment was performed 6 hours later via arterial injection. Functional and histological analyses were performed 24 hours, 48 hours and 2 months after treatment using serum creatinine, urine protein to creatinine ratio, inflammatory and regeneration markers and histomorphometric analysis of the kidney. Statistical analysis was performed by analysis of variance followed by the Tukey’s test for multiple comparisons or by nonparametric Kruskal-Wallis followed by Dunn. Statistical significance level was defined as p <0.05.ResultshAFSCs treatment resulted in significantly reduced serum creatinine level at 24 hours, less tubular necrosis, less hyaline cast formation, higher proliferation index, less inflammatory cell infiltration and less myofibroblasts at 48h. The treated group had less fibrosis and proteinuria at 2 months after injury.ConclusionhAFSCs contain a renal progenitor cell subpopulation that has a nephroprotective effect when delivered intra-arterially in rats with renal I/R injury, and reduces interstitial fibrosis on long term follow-up.

Stem/Stromal Cells for Treatment of Kidney Injuries With Focus on Preclinical Models

“…Authors agree that the higher the dose, the worse the outcome, mostly due to cell emboli formation. The optimal cell concentration range found is 5 × 10 5 − 1 × 10 6 ( 164 , 231 ).…”

“…I/R injury eventually leads to kidney fibrosis, which is the deposition of connective tissue in the renal parenchyma. Studies using hiPSC with renal lineage and amniotic fluid-derived stem cells (AFSC) revealed a decrease in interstitial fibrosis and myofibroblast formation ( 164 , 165 ). In another study using hWJ-MSC the reduction of overall fibrosis was attributed to a HGF/TGF-β shift to HGF ( 170 ).…”

Ischemia-Reperfusion Injury Reduces Long Term Renal Graft Survival: Mechanism and Beyond

“…MSC-mediated microvesicle release has also been shown to enhance cell survival and attenuate programmed cell death processes ( Bruno et al, 2012 , 2009 ). Overall, numerous studies have demonstrated that exogenous administration of MSCs attenuates renal ischemia-reperfusion injury ( Du et al, 2013 ; Bruno et al, 2009 ; Togel et al, 2005a ; Jiang et al, 2015 ; Duffield and Bonventre, 2005 ; Monteiro Carvalho Mori Da Cunha et al, 2015 ; Duffield et al, 2005 ) and, therefore, may be a potential future renoprotective strategy.…”

Urine of Preterm Neonates as a Novel Source of Kidney Progenitor Cells

“…These cells presented anti-inflammatory and antiapoptotic effects and inhibited fibrosis in an ischemia-reperfusion model in rats. 14 Because stem/progenitor cells from specific adult tissue generally present limited differentiation potential and its existence in the adult kidney is questionable, preterm neonatal urinary cells (born before completion of nephrogenesis) might be a tissue-specific potent source of progenitors with higher potential compared with adult cells.…”