Therapeutic Effects of Human Amniotic Fluid-Derived Stem Cells on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction

Dong Sun,Xudong Zhou,Xiaoju Li,Aiguo Xiao,Zhongcheng Yin,Lin Bu,Caixia Liu,Christos Chatziantoniou

doi:10.1371/journal.pone.0065042

Abstract

Interstitial fibrosis is regarded as the main pathway for the progression of chronic kidney disease (CKD) and is often associated with severe renal dysfunction. Stem cell-based therapies may provide alternative approaches for the treatment of CKD. Human amniotic fluid-derived stem cells (hAFSCs) are a novel stem cell population, which exhibit both embryonic and mesenchymal stem cell characteristics. Herein, the present study investigated whether the transplantation of hAFSCs into renal tissues could improve renal interstitial fibrosis in a murine model of unilateral ureteral obstruction (UUO). We showed that hAFSCs provided a protective effect and alleviated interstitial fibrosis as reflected by an increase in microvascular density; additionally, hAFSCs treatment beneficially modulated protein levels of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α) and transforming growth factor-β1 (TGF-β1). Therefore, we hypothesize that hAFSCs could represent an alternative, readily available source of stem cells that can be applied for the treatment of renal interstitial fibrosis.

Highlights

Chronic kidney disease (CKD), which affects individual worldwide [1,2], is recognized as a major public health problem
Interstitial fibrosis is regarded as the main pathway for CKD progression, which culminates in end-stage renal failure
HAFSCs stained positive for Oct-4, a surface marker present on stem cells (Figure 1D)

Summary

Introduction

Chronic kidney disease (CKD), which affects individual worldwide [1,2], is recognized as a major public health problem. Despite the great deal of effort invested in identifying therapies for CKD, the number of patients requiring dialysis and kidney replacement continues to rise [3]. The current treatment modalities and donor kidney availability are insufficient, further increasing the demand for new available approaches to treat chronic nephropathy. Stem cells have become a promising therapeutic tool for the treatment of kidney diseases [4,5,6,7]. Several groups have demonstrated that bone marrow-derived mesenchymal stem cells (MSCs) contributed to regeneration following renal injury [8,9,10,11]

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Results

Conclusion