title: Mesenchymal-like progenitors derived from human embryonic stem cells promote recovery from acute kidney injury via paracrine actions.
abstract: OBJECTIVE
  The engraftment of mesenchymal stem cells (MSCs) is reported to promote recovery of renal function in animal models of acute kidney injury (AKI). However, it is unknown whether mesenchymal-like progenitors (MPs) derived from human embryonic stem cells (hESCs) can mediate similar therapeutic effects. We investigated the responses of recipient renal tissue to engraftment of hESC-MPs and underlying mechanisms of these effects.
  
  
  METHODS
  We measured blood urea nitrogen and creatinine levels of AKI mice with hESC-MPs transplantation and control mice. We performed renal morphology analysis by immunohistochemistry and electron microscopy to confirm the renoprotective effects of engrafted hESC-MPs. Proliferation, apoptosis and gene expression of tubular cells were also monitored by immunohistochemistry and real-time quantitative polymerase chain reaction to investigate the mechanisms that occurred.
  
  
  RESULTS
  After transplantation of hESC-MPs into mice with cisplatin-induced AKI, improvements in renal function and recovery from tubular epithelial cell injury were observed. Engrafted hESC-MPs were localized to areas of injured kidney 5 days after cisplatin induction, where they promoted tubular cell proliferation and decreased kidney cell apoptosis. The beneficial effect was further confirmed by the capability of the engrafted cells to up-regulate renal gene expression of anti-inflammatory cytokines and pro-survival cytokines. Meanwhile, infusion of these cells reduced renal gene expression of pro-inflammatory cytokines and monocyte chemotactic protein-1, a chemokine that stimulates monocyte and macrophage infiltration.
  
  
  CONCLUSIONS
  Our results show that infused hESC-MPs may promote recovery from AKI by regulating related cytokines.
authors: College of Life Sciences, Zhejiang University, Hangzhou, China.
authors: Jingfeng
authors: J
authors: Luo
authors: Xiaoli
authors: X
authors: Zhao
authors: Zhou
authors: Z
authors: Tan
authors: Zhongyuan
authors: Z
authors: Su
authors: Feilong
authors: F
authors: Meng
authors: Ming
authors: M
authors: Zhang
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001806:Blood Urea Nitrogen; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology; D005786:Gene Expression Regulation; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D019899:Paracrine Communication
chemical_list: D016207:Cytokines; D003404:Creatinine; D002945:Cisplatin