Abstract: FR-PO365

Transplantation of Amniotic Fluid-Derived Stem Cells Preconditioned with Glial Cell Line–Derived Neurotrophic Factor Alleviates Renal Interstitial Fibrosis

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Sun, Dong, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
  • Li, Shulin, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
  • Zhao, yuan, Xuzhou Medical University, Xuzhou, China
  • Wang, Zhuojun, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
  • Wang, Jia, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
  • Liu, Caixia, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
Background

The aim of the present study was to determine whether transplantation of glial cell line–derived neurotrophic factor (GDNF)–modified AFSCs is more useful than transplantation of unmodified AFSCs for the treatment of renal interstitial fibrosis.

Methods

A unilateral ureteral obstruction (UUO) model was established in mice. Either GDNF-AFSCs or AFSCs were transplanted into nu/nu mice via their caudal veins. The 48 mice (12 each group) were randomly assigned to sham-operation group (sham), UUO-saline solution group (UUO), AFSCs transplantation group (AFSCs) and GDNF-modified AFSCs transplantation group (GDNF-AFSCs) . GFP fluorescent staining was used for the frozen sections in order to track the transplated AFSCs in the kidney under a fluorescence microscope. The oxidative , inflammatory , endothelial and mitochondrial makers were measured after 3 and 7 days transplantation.

Results

GDNF-AFSCs noticeably suppressed oxidative stress and inflammation; additionally, GDNF-AFSCs positively regulated peritubular capillaries (PTCs), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α (HIF-1α), transforming growth factor-β1 (TGF-β1) protein levels and mitochondrial factors.

Conclusion

GDNF promotes the abilities of AFSCs to inhibit inflammatory and oxidative stress effects, repair renal microvessels, relieve tissue hypoxia and mitochondrial damage and alleviate renal interstitial fibrosis.

A. Culture of AFSCs, lentivirus vector transfection and immunofluorescent localization of frozen section in AFSC transplanted kidney.
(B-D). Immunohistochemical staining (40×) and Western blot analysis of oxidative, inflammatory and endothelial markers.

Funding

  • Government Support - Non-U.S.