Peripheral blood-derived endothelial progenitor cell therapy prevented deterioration of chronic kidney disease in rats

Tien Hung Huang, Yen Ta Chen, Pei Hsun Sung, Hsin Ju Chiang, Yung Lung Chen, Han Tan Chai, Sheng Ying Chung, Tzu Hsien Tsai, Chih Chao Yang, Chih Hung Chen, Yi Ling Chen, Hsueh Wen Chang, Cheuk Kwan Sun, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

39 Scopus citations

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. Methods and 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 × 105) and penile vein (6.7 × 105) injections by day 14 after CKD induction]. By day 60, kidney blood fow (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), infammatory (TNF-α, MMP-9), oxidative-stress (oxidized protein, NOX-1), fbrotic (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 fow 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). Conclusion: The results support that PBDEPC therapy effectively inhibits the propagation of CKD and the deterioration of renal function through enhancement of angiogenesis, blood fow, and anti-oxidative capacity as well as suppression of infammation, oxidative stress, apoptosis, and fbrosis in a rodent model.

Original languageEnglish
Pages (from-to)804-824
Number of pages21
JournalAmerican Journal of Translational Research
Volume7
Issue number5
StatePublished - 07 07 2015

Bibliographical note

Publisher Copyright:
© 2015, E-Century Publishing Corporation. All Rights Reserved.

Keywords

  • 5/6 nephrectomy
  • Angiogenesis
  • Apoptosis
  • Chronic kidney disease
  • Infammation
  • Oxidative stress

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