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

PLoS One. 2015 Aug 21;10(8):e0136145. doi: 10.1371/journal.pone.0136145. eCollection 2015.

Abstract

Objectives: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / therapy*
  • Amniotic Fluid / cytology*
  • Animals
  • Cell Differentiation
  • Cell Tracking
  • Cells, Cultured
  • Female
  • Humans
  • Kidney / cytology*
  • Kidney / pathology
  • Male
  • Pregnancy
  • Rats, Wistar
  • Reperfusion Injury / pathology
  • Reperfusion Injury / therapy*
  • Stem Cell Transplantation*
  • Stem Cells / cytology*

Grant support

Research was funded by the Agency for Innovation by Science and technology (IWT)-Vlaanderen, by the European Commission grant of Diagnostic Molecular Imaging (DIMI) (LSHB11 CT-2005-512146) and by the In vivo Molecular Imaging Research (IMIR) program from the KU Leuven. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.