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

诱导性多能干细胞衍生的间充质干细胞疗法有效保护肾脏免受急性缺血再灌注损伤

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作者: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

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 SD-rats (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-tubular-integrity (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.

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