Fetal kidney stem cells ameliorate cisplatin induced acuterenal failure and promote renal angiogenesis

• 来源期刊: 世界干细胞杂志：英文版（电子版）
• 学科: 医学
• 关键词: Fetal kidney STEM cells Mesenchymal andrenal PROGENITOR markers ACUTE RENAL failure STEM celltherapy ANGIOGENESIS
• 年，卷（期）: 2015,（4）
• 页码范围: 776-788
• 页数: 13页
• 分类号: R

摘要

AIM To investigate whether fetal kidney stem cells（fKSC） ameliorate cisplatin induced acute renal failure（ARF） in rats and promote renal angiogenesis.METHODS： The fKSC were isolated from rat fetusesof gestation day 16 and expanded in vitro up to 3rdpassage. They were characterized for the expressionof mesenchymal and renal progenitor markers by flowcytometry and immunocytochemistry, respectively.The in vitro differentiation of fKSC towards epitheliallineage was evaluated by the treatment with specificinduction medium and their angiogenic potential bymatrigel induced tube formation assay. To study theeffect of fKSC in ARF, fKSC labeled with PKH26 wereinfused in rats with cisplatin induced ARF and, the bloodand renal tissues of the rats were collected at differenttime points. Blood biochemical parameters werestudied to evaluate renal function. Renal tissues wereevaluated for renal architecture, renal cell proliferationand angiogenesis by immunohistochemistry, renal cellapoptosis by terminal deoxynucleotidyl transferase nickendlabeling assay and early expression of angiogenicmolecules viz . vascular endothelial growth factor （VEGF）,hypoxia-inducible factor （HIF）-1α and endothelial nitricoxide synthase （eNOS） by western blot.RESULTS： The fKSC expressed mesenchymal markersviz . CD29, CD44, CD73, CD90 and CD105 as well as renal progenitor markers viz . Wt1, Pax2 and Six2. Theyexhibited a potential to form CD31 and Von Willebrandfactor expressing capillary-like structures and could bedifferentiated into cytokeratin （CK）18 and CK19 positiveepithelial cells. Administration of fKSC in rats with ARF ascompared to administration of saline alone, resulted in asignificant improvement in renal function and histology onday 3 （2.33 ± 0.33 vs 3.50 ± 0.34, P 〈 0.05） and on day7 （0.83 ± 0.16 vs 2.00 ± 0.25, P 〈 0.05）. The infusedPKH26 labeled fKSC were observed to engraft in damagedrenal tubules and showed increased proliferation andreduced apoptosis （P 〈 0.05） of renal cells. The k