title: Delayed treatment with human umbilical cord blood-derived stem cells attenuates diabetic renal injury.
abstract: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Excess accumulation of extracellular matrix and the epithelial-to-mesenchymal transition contribute to renal fibrosis, which is associated with DKD. The present study examined whether delayed treatment with human umbilical cord blood-derived stem cells (hUCB-SC) showed a therapeutic effect on DKD progression. Experimental diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 50 mg/kg) into 6-week-old male Sprague-Dawley rats. Age-matched control rats received an equivalent volume of sodium citrate buffer alone. At 4 weeks after the STZ injection when diabetic renal injury had developed, hUCB-SC were administered (1 × 10(6) cells/rat) through the tail vein. Four weeks after administering the hUCB-SC, rats were sacrificed and we measured indices of DKD, including urinary protein excretion as well as fibronectin, α-smooth muscle actin (α-SMA), and E-cadherin mRNA, and protein expression. Diabetic rats developed significantly increased urinary protein excretion and renal hypertrophy compared to those in control rats. Renal expression of fibronectin and α-SMA mRNA, and protein were increased significantly in diabetic rats compared to those in the controls. E-cadherin protein expression in diabetic kidneys decreased significantly. Intravenously administered hUCB-SC effectively reduced proteinuria, renal fibronectin, and α-SMA up-regulation, as well as renal E-cadherin down-regulation in diabetic rats without a significant effect on blood glucose. Engrafted hUCB-SC in diabetic kidneys were confirmed by human DNA PKcs. The results demonstrated that delayed treatment with hUCB-SC attenuated the progression of diabetic renal injury.
authors.affiliation: Department of Bioinspired Science, Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Park
authors.forename: J
authors.initials: J
authors.lastname: Park
authors.forename: S H
authors.initials: SH
authors.lastname: Hwang
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.forename: H
authors.initials: H
authors.lastname: Ha
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002470:Cell Survival; D036101:Cord Blood Stem Cell Transplantation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D006085:Graft Survival; D006801:Humans; D006984:Hypertrophy; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000199:Actins; D015415:Biomarkers; D019040:E-Selectin; D005353:Fibronectins; D012333:RNA, Messenger; C498862:Acta2 protein, rat