title: Amniotic Fluid Derived Stem Cells with a Renal Progenitor Phenotype Inhibit Interstitial Fibrosis in Renal Ischemia and Reperfusion Injury in Rats.
abstract: OBJECTIVE
  Mesenchymal 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  hAFSCs 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 48 h. The treated group had less fibrosis and proteinuria at 2 months after injury.
  
  
  CONCLUSIONS
  hAFSCs 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.
authors: Department of Development and Regeneration, Organ System Cluster, Fetal therapy group, Group Biomedical Sciences, KU Leuven, Leuven, Belgium; Experimental Veterinary Surgery Laboratory, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: Marina Gabriela
authors: MG
authors: Monteiro Carvalho Mori da Cunha
authors: Department of Development and Regeneration, Organ System Cluster, Fetal therapy group, Group Biomedical Sciences, KU Leuven, Leuven, Belgium.
authors: Silvia
authors: S
authors: Zia
authors: Department of Development and Regeneration, Organ System Cluster, Laboratory of Pediatric Nephrology, Group Biomedical Sciences, KU Leuven, Leuven, Belgium.
authors: Fanny
authors: F
authors: Oliveira Arcolino
authors: Department of Pharmaceutical and Pharmacological Sciences, Laboratory of Molecular Virology and Gene Therapy, Group Biomedical Sciences, KU Leuven, Leuven, Belgium.
authors: Marianne Sylvia
authors: MS
authors: Carlon
authors: Experimental Veterinary Surgery Laboratory, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: Diego Vilibaldo
authors: DV
authors: Beckmann
authors: Experimental Veterinary Surgery Laboratory, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: Ney Luis
authors: NL
authors: Pippi
authors: Experimental Veterinary Surgery Laboratory, Universidade Federal de Santa Maria, Santa Maria, Brazil.
authors: Dominguita
authors: D
authors: Luhers Graça
authors: Department of Development and Regeneration, Organ System Cluster, Laboratory of Pediatric Nephrology, Group Biomedical Sciences, KU Leuven, Leuven, Belgium; Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
authors: Elena
authors: E
authors: Levtchenko
authors: Department of Development and Regeneration, Organ System Cluster, Fetal therapy group, Group Biomedical Sciences, KU Leuven, Leuven, Belgium; Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium.
authors: Jan
authors: J
authors: Deprest
authors: Department of Development and Regeneration, Organ System Cluster, Fetal therapy group, Group Biomedical Sciences, KU Leuven, Leuven, Belgium; Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
authors: Jaan
authors: J
authors: Toelen
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000628:therapy*; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D058948:Cell Tracking; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000473:pathology; D008297:Male; D011247:Pregnancy; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*