title: The alleviation of acute and chronic kidney injury by human Wharton's jelly-derived mesenchymal stromal cells triggered by ischemia-reperfusion injury via an endocrine mechanism.
abstract: OBJECTIVE
  The effects of human Wharton's jelly-derived mesenchymal stromal cells (WJ-MSC) on acute and chronic kidney injury induced by ischemia-reperfusion injury (IRI) were assessed.
  
  
  METHODS
  WJ-MSC were injected intravenously immediately after solitary kidney ischemia for 45 min. Cells were labeled with 5-bromo-2'deoxy-uridine (BrdU) for tracing in vivo. At 48 h post-IRI, serum creatinine and blood urea nitrogen (BUN) were measured. Tubular cell proliferation and apoptosis as well as activation of the Akt signal were identified by immunostaining. Real-time polymerase chain reaction (PCR) was employed to determine gene expression of inflammation-related cytokines and hepatocyte growth factor (HGF). Levels of human HGF were assayed by enzyme-linked immunosorbant assay (ELISA). Twenty-two weeks later, renal fibrosis was assessed by Masson's tri-chrome staining, collagen content and α-smooth muscle actin (α-SMA) staining.
  
  
  RESULTS
  There was no sign of labeled cells residing in the damaged kidney. Acute renal dysfunction elicited by IRI was considerably improved by WJ-MSC, in parallel with a stronger proliferative response and less apoptotic events. Additionally, phosphoAkt staining in injured tubular cells was substantially intensified. Cell treatment also caused a remarkable up-regulation of kidney interleukin (IL)-10, heme oxygenase (HO)-1 and HGF expression. Human HGF was detected in cell supernatants and the serum of cell-infused rats. Moreover, IRI-initiated fibrosis was abrogated by cell therapy, coincident with function amelioration.
  
  
  CONCLUSIONS
  WJ-MSC alleviate acute kidney injury, thereby rescuing the ensuing fibrotic lesions in an endocrine manner. The Akt signal in impaired tubular cells is reinforced by WJ-MSC, facilitating cell resistance to apoptosis and cell proliferation. HGF, either delivered or induced by WJ-MSC, is an important contributor.
authors.affiliation: Department of Urology, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.forename: Xin-Feng
authors.initials: XF
authors.lastname: Zhao
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Ying-Jian
authors.initials: YJ
authors.lastname: Zhu
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Liu
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001806:Blood Urea Nitrogen; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D003404:Creatinine / Q000097:blood; D004703:Endocrine System / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D015427:Reperfusion Injury / Q000097:blood / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016753:Interleukin-10; D017228:Hepatocyte Growth Factor; D003404:Creatinine; D051547:Heme Oxygenase-1; D051057:Proto-Oncogene Proteins c-akt