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

• Published in: Cell transplantation 2019-01, Vol.28 (1), p.65-78
• Main Authors: Li, Shulin, Zhao, Yuan, Wang, Zhuojun, Wang, Jia, Liu, Caixia, Sun, Dong
• Format: Article
• Language: English
• Subjects: Amniotic fluid; Amniotic Fluid - cytology; Animals; Blotting, Western; Capillaries; Cells, Cultured; Female; Fibrosis; Fibrosis - drug therapy; Fibrosis - therapy; Fluorescent Antibody Technique; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - pharmacology; Growth factors; Humans; Hypoxia; Immunohistochemistry; Inflammation; Kidney Diseases - drug therapy; Kidney Diseases - therapy; Lentivirus - genetics; Mesenchyme; Mice; Microscopy, Electron, Transmission; Mitochondria; Neuronal-glial interactions; Original; Oxidative stress; Pregnancy; Stem cell transplantation; Stem cells; Stem Cells - cytology; Stem Cells - physiology; Surgery; Transforming growth factor-b1; Transmission electron microscopy; Vascular endothelial growth factor
• ISSN: 0963-6897; 1555-3892
• DOI: 10.1177/0963689718815850

Amniotic fluid-derived stem cells (AFSCs), which exhibit both embryonic and mesenchymal stem cell characteristics, have been shown to mitigate the degree of renal interstitial fibrosis. 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. Mice were randomly assigned to a sham-operation group (sham), a unilateral ureteral obstruction (UUO)-saline solution group (UUO), an AFSC transplantation group (AFSC) and a GDNF-modified AFSC transplantation group (GDNF-AFSC) and sacrificed at days 3 and 7 post-surgery (six in each group). We showed that 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), and transforming growth factor-β1 (TGF-β1) protein levels. Transmission electron microscopy (TEM) revealed that mitochondrial injury induced by the UUO model was significantly ameliorated after the mice were treated with GDNF-AFSCs. Therefore, we determined that GDNF gene promotes the abilities of AFSCs to inhibit inflammatory and oxidative stress effects, repair renal microvessels, relieve tissue hypoxia and mitochondrial damage, and, ultimately, alleviate renal interstitial fibrosis.