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

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 journal › Journal Article › peer-review

22 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 language	English
Article number	AJTR0076837
Pages (from-to)	3053-3067
Number of pages	15
Journal	American Journal of Translational Research
Volume	10
Issue number	10
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

Ko, S. F., Chen, Y. T., Wallace, C. G., Chen, K. H., Sung, P. H., Cheng, B. C., Huang, T. H., Chen, Y. L., Li, Y. C., Chang, H. W., Lee, M. S., Yang, C. C., & Yip, H. K. (2018). Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury. American Journal of Translational Research, 10(10), 3053-3067. Article AJTR0076837.

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

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.",

keywords = "Acute kidney ischemia reperfusion injury, Inducible pluripotent stem cell, Inflammation, Mesenchymal stem cell, Oxidative stress",

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

year = "2018",

language = "英语",

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journal = "American Journal of Translational Research",

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Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury. / Ko, Sheung Fat; Chen, Yen Ta; Wallace, Christopher Glenn et al.
In: American Journal of Translational Research, Vol. 10, No. 10, AJTR0076837, 2018, p. 3053-3067.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Inducible pluripotent stem cell-derived mesenchymal stem cell therapy effectively protected kidney from acute ischemia-reperfusion injury

AU - Ko, Sheung Fat

AU - Chen, Yen Ta

AU - Wallace, Christopher Glenn

AU - Chen, Kuan Hung

AU - Sung, Pei Hsun

AU - Cheng, Ben Chung

AU - Huang, Tien Hung

AU - Chen, Yi Ling

AU - Li, Yi Chen

AU - Chang, Hsueh Wen

AU - Lee, Mel S.

AU - Yang, Chih Chao

AU - Yip, Hon Kan

PY - 2018

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N2 - 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.

AB - 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.

KW - Acute kidney ischemia reperfusion injury

KW - Inducible pluripotent stem cell

KW - Inflammation

KW - Mesenchymal stem cell

KW - Oxidative stress

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M3 - 文章

C2 - 30416650

AN - SCOPUS:85056165014

SN - 1943-8141

VL - 10

SP - 3053

EP - 3067

JO - American Journal of Translational Research

JF - American Journal of Translational Research

IS - 10

M1 - AJTR0076837

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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