Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury

Sheung Fat Ko, Yen Ta Chen, Christopher Glenn Wallace, Kuan Hung Chen, Pei Hsun Sung, Ben Chung Cheng, Tien Hung Huang, Yi Ling Chen, Yi Chen Li, Hsueh Wen Chang, Mel S. Lee, Chih Chao Yang, Hon Kan Yip*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

21 Scopus citations

Abstract

This study tested whether inducible pluripotent stem cell (iPSC)-derived mesenchymal stem cell (MSC) therapy could effectively protect kidney from acute ischemia (1 h)-reperfusion (5 day) injury (IRI). Male-adult SDrats (n = 24) were equally categorized into groups 1 (sham-control), 2 [sham-control + iPSC-MSC (1.2 × 106 cells/ rat)], 3 (IR only) and 4 (IR + iPSC-MSC). Blood urine nitrogen/creatinine levels and ratio of urine protein to creatinine, kidney weight and expressions of inflammation (TNF-α/NF-κB), oxidative-stress (NOX-1/NOX-2/oxidized protein) and apoptosis (mitochondrial-Bax/cleaved caspase-3/PARP) were significantly higher in group 3 than in groups 1, 2 and 4 and significantly higher in group 4 than in groups 1 and 2 (all P<0.0001), but showed no differences between groups 1 and 2, whereas the protein expressions of anti-inflammation (IL-4/IL-10) and endothelial (CD31/vWF) markers exhibited an opposite pattern to inflammation among the four groups (all P<0.0001). Protein expressions of angiogenesis (VEGF/CXCR4/SDF-1α) markers progressively increased from groups 1 to 4 (all P<0.0001). Cellular expressions of kidney injury score/DNA-damage (γ-H2AX)/apoptotic nuclei and glomerulus-tubular-damage (KIM/FSP-1) displayed an identical pattern to inflammation, whereas the cellular expressions of glomerulus-tubularintegrity (dystroglycan/podocin/p-cadherin/synaptopodin/ZO-1/fibronectin) revealed an opposite pattern to inflammation among the four groups (all P<0.0001). In conclusion, iPSC-derived MSC therapy effectively protected kidney against IRI.

Original languageEnglish
Article numberAJTR0076837
Pages (from-to)3053-3067
Number of pages15
JournalAmerican Journal of Translational Research
Volume10
Issue number10
StatePublished - 2018

Bibliographical note

Publisher Copyright:
© 2018, E-Century Publishing Corporation. All rights reserved.

Keywords

  • Acute kidney ischemia reperfusion injury
  • Inducible pluripotent stem cell
  • Inflammation
  • Mesenchymal stem cell
  • Oxidative stress

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