title: Peripheral blood-derived endothelial progenitor cell therapy prevented deterioration of chronic kidney disease in rats.
abstract: BACKGROUND
  This study tested the hypothesis that peripheral blood-derived endothelial progenitor cell (PBDEPC) therapy can impede the deterioration of chronic kidney disease (CKD) induced by 5/6 nephrectomy in rats.
  
  
  RESULTS
  Adult-male rats (n = 30) were equally categorized into group 1 (sham control), group 2 (CKD only) and group 3 [CKD + PBDEPC (left intra-arterial (3.3 × 10(5)) and penile vein (6.7 × 10(5)) injections by day 14 after CKD induction]. By day 60, kidney blood flow (KBF) was significantly lower in group 2 than that in groups 1 and 3, and significantly lower in group 3 than that in group 1, whereas the levels of serum creatinine, and kidney injury score and size showed an opposite pattern compared to that of KBF among all groups (all p < 0.001). Protein expressions of apoptotic (caspase 3, PARP), inflammatory (TNF-α, MMP-9), oxidative-stress (oxidized protein, NOX-1), fibrotic (Smad3, TGF-β), and hypoxic/ischemic cell-stress (HIF-1α, p-Akt) biomarkers showed an opposite pattern, whereas angiogenesis at protein (eNOS, CD31) and cellular (CD31+, CXCR4+) levels showed an identical pattern compared to that of blood flow in all groups (all p < 0.01). Other pro-angiogenic biomarkers (SDF-1α, CXCR4, VEGF) at protein and cellular levels and antioxidants (HO-1+, NQO 1, GR+) at cellular level showed progressive significant increase from groups 1 to 3 (all p < 0.001).
  
  
  CONCLUSIONS
  The results support that PBDEPC therapy effectively inhibits the propagation of CKD and the deterioration of renal function through enhancement of angiogenesis, blood flow, and anti-oxidative capacity as well as suppression of inflammation, oxidative stress, apoptosis, and fibrosis in a rodent model.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Tien-Hung
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Yen-Ta
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Sung
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Hsin-Ju
authors.initials: HJ
authors.lastname: Chiang
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Chung
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Division of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, National Sun Yat-Sen University Kaohsiung, 83301, Taiwan.
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Department of Emergency Medicine, E-DA Hospital, I-Shou University Kaohsiung, 82445, Taiwan.
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan ; Center for Shock Wave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan ; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, 83301, Taiwan ; Medical University Hospital, China Medical University Taichung, 40402, Taiwan.
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
keywords: 5/6 nephrectomy; Chronic kidney disease; angiogenesis; apoptosis; inflammation; oxidative stress