Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury

Kun Chen Lin; Hon Kan Yip; Pei Lin Shao; Shun Cheng Wu; Kuan Hung Chen; Yen Ta Chen; Chih Chao Yang; Cheuk Kwan Sun; Gour Shenq Kao; Sheng Yi Chen; Han Tan Chai; Chia Lo Chang; Chih Hung Chen; Mel S. Lee

doi:10.1016/j.ijcard.2016.04.061

Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury

Kun Chen Lin, Hon Kan Yip, Pei Lin Shao, Shun Cheng Wu, Kuan Hung Chen, Yen Ta Chen, Chih Chao Yang, Cheuk Kwan Sun, Gour Shenq Kao, Sheng Yi Chen, Han Tan Chai, Chia Lo Chang, Chih Hung Chen, Mel S. Lee^*

^*Corresponding author for this work

School of Medicine

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

200 Scopus citations

Abstract

Background In this study, we tested the hypothesis that a combined adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy protected rat kidney from acute ischemia-reperfusion (IR) injury (i.e., ligation of both renal arteries for 1 h and reperfusion for 72 h prior to euthanization). Methods and results Adult-male SD rats (n = 40) were equally categorized into group 1 (sham control), group 2 (IR), group 3 [IR + exosome (100 μg)], group 4 [IR + ADMSC (1.2 × 10⁶ cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3 h after IR procedure from venous administration. By 72 h, the creatinine level and kidney injury score were the lowest in group 1 and the highest in group 2, significantly higher in group 3 than in groups 4 and 5, and significantly higher in group 4 than in group 5 (all P < 0.0001). The protein expression of inflammatory (TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-β) biomarkers showed an identical pattern, whereas the anti-apoptotic (Smad1/5, BMP-2) and angiogenesis (CD31/vWF/angiopoietin) biomarkers and mitochondrial cytochrome-C showed an opposite pattern of creatinine level among the five groups (all P < 0.001). The microscopic findings of glomerular-damage (WT-1), renal tubular-damage (KIM-1), DNA-damage (γ-H2AX), inflammation (MPO/MIF/CD68) exhibited an identical pattern, whereas the podocyte components (podocin/p-cadherin/synaptopodin) displayed a reversed pattern of creatinine level (all P < 0.0001). Conclusion Combined exosome-ADMSC therapy was superior to either one for protecting kidney from acute IR injury.

Original language	English
Pages (from-to)	173-185
Number of pages	13
Journal	International Journal of Cardiology
Volume	216
DOIs	https://doi.org/10.1016/j.ijcard.2016.04.061
State	Published - 01 08 2016

Bibliographical note

Publisher Copyright:
© 2016 Published by Elsevier Ireland Ltd.

Keywords

Acute kidney ischemia-reperfusion injury
Adipose-derived mesenchymal stem cell
Exosome
Inflammation
Oxidative stress

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Lin, K. C., Yip, H. K., Shao, P. L., Wu, S. C., Chen, K. H., Chen, Y. T., Yang, C. C., Sun, C. K., Kao, G. S., Chen, S. Y., Chai, H. T., Chang, C. L., Chen, C. H., & Lee, M. S. (2016). Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury. International Journal of Cardiology, 216, 173-185. https://doi.org/10.1016/j.ijcard.2016.04.061

@article{b88ff7b3856a405d921a40360ddeea65,

title = "Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury",

abstract = "Background In this study, we tested the hypothesis that a combined adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy protected rat kidney from acute ischemia-reperfusion (IR) injury (i.e., ligation of both renal arteries for 1 h and reperfusion for 72 h prior to euthanization). Methods and results Adult-male SD rats (n = 40) were equally categorized into group 1 (sham control), group 2 (IR), group 3 [IR + exosome (100 μg)], group 4 [IR + ADMSC (1.2 × 106 cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3 h after IR procedure from venous administration. By 72 h, the creatinine level and kidney injury score were the lowest in group 1 and the highest in group 2, significantly higher in group 3 than in groups 4 and 5, and significantly higher in group 4 than in group 5 (all P < 0.0001). The protein expression of inflammatory (TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-β) biomarkers showed an identical pattern, whereas the anti-apoptotic (Smad1/5, BMP-2) and angiogenesis (CD31/vWF/angiopoietin) biomarkers and mitochondrial cytochrome-C showed an opposite pattern of creatinine level among the five groups (all P < 0.001). The microscopic findings of glomerular-damage (WT-1), renal tubular-damage (KIM-1), DNA-damage (γ-H2AX), inflammation (MPO/MIF/CD68) exhibited an identical pattern, whereas the podocyte components (podocin/p-cadherin/synaptopodin) displayed a reversed pattern of creatinine level (all P < 0.0001). Conclusion Combined exosome-ADMSC therapy was superior to either one for protecting kidney from acute IR injury.",

keywords = "Acute kidney ischemia-reperfusion injury, Adipose-derived mesenchymal stem cell, Exosome, Inflammation, Oxidative stress",

author = "Lin, {Kun Chen} and Yip, {Hon Kan} and Shao, {Pei Lin} and Wu, {Shun Cheng} and Chen, {Kuan Hung} and Chen, {Yen Ta} and Yang, {Chih Chao} and Sun, {Cheuk Kwan} and Kao, {Gour Shenq} and Chen, {Sheng Yi} and Chai, {Han Tan} and Chang, {Chia Lo} and Chen, {Chih Hung} and Lee, {Mel S.}",

note = "Publisher Copyright: {\textcopyright} 2016 Published by Elsevier Ireland Ltd.",

year = "2016",

month = aug,

day = "1",

doi = "10.1016/j.ijcard.2016.04.061",

language = "英语",

volume = "216",

pages = "173--185",

journal = "International Journal of Cardiology",

issn = "0167-5273",

publisher = "Elsevier Ireland Ltd",

}

Lin, KC, Yip, HK, Shao, PL, Wu, SC, Chen, KH, Chen, YT, Yang, CC, Sun, CK, Kao, GS, Chen, SY, Chai, HT, Chang, CL, Chen, CH & Lee, MS 2016, 'Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury', International Journal of Cardiology, vol. 216, pp. 173-185. https://doi.org/10.1016/j.ijcard.2016.04.061

TY - JOUR

T1 - Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury

AU - Lin, Kun Chen

AU - Yip, Hon Kan

AU - Shao, Pei Lin

AU - Wu, Shun Cheng

AU - Chen, Kuan Hung

AU - Chen, Yen Ta

AU - Yang, Chih Chao

AU - Sun, Cheuk Kwan

AU - Kao, Gour Shenq

AU - Chen, Sheng Yi

AU - Chai, Han Tan

AU - Chang, Chia Lo

AU - Chen, Chih Hung

AU - Lee, Mel S.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Background In this study, we tested the hypothesis that a combined adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy protected rat kidney from acute ischemia-reperfusion (IR) injury (i.e., ligation of both renal arteries for 1 h and reperfusion for 72 h prior to euthanization). Methods and results Adult-male SD rats (n = 40) were equally categorized into group 1 (sham control), group 2 (IR), group 3 [IR + exosome (100 μg)], group 4 [IR + ADMSC (1.2 × 106 cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3 h after IR procedure from venous administration. By 72 h, the creatinine level and kidney injury score were the lowest in group 1 and the highest in group 2, significantly higher in group 3 than in groups 4 and 5, and significantly higher in group 4 than in group 5 (all P < 0.0001). The protein expression of inflammatory (TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-β) biomarkers showed an identical pattern, whereas the anti-apoptotic (Smad1/5, BMP-2) and angiogenesis (CD31/vWF/angiopoietin) biomarkers and mitochondrial cytochrome-C showed an opposite pattern of creatinine level among the five groups (all P < 0.001). The microscopic findings of glomerular-damage (WT-1), renal tubular-damage (KIM-1), DNA-damage (γ-H2AX), inflammation (MPO/MIF/CD68) exhibited an identical pattern, whereas the podocyte components (podocin/p-cadherin/synaptopodin) displayed a reversed pattern of creatinine level (all P < 0.0001). Conclusion Combined exosome-ADMSC therapy was superior to either one for protecting kidney from acute IR injury.

AB - Background In this study, we tested the hypothesis that a combined adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy protected rat kidney from acute ischemia-reperfusion (IR) injury (i.e., ligation of both renal arteries for 1 h and reperfusion for 72 h prior to euthanization). Methods and results Adult-male SD rats (n = 40) were equally categorized into group 1 (sham control), group 2 (IR), group 3 [IR + exosome (100 μg)], group 4 [IR + ADMSC (1.2 × 106 cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3 h after IR procedure from venous administration. By 72 h, the creatinine level and kidney injury score were the lowest in group 1 and the highest in group 2, significantly higher in group 3 than in groups 4 and 5, and significantly higher in group 4 than in group 5 (all P < 0.0001). The protein expression of inflammatory (TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-β) biomarkers showed an identical pattern, whereas the anti-apoptotic (Smad1/5, BMP-2) and angiogenesis (CD31/vWF/angiopoietin) biomarkers and mitochondrial cytochrome-C showed an opposite pattern of creatinine level among the five groups (all P < 0.001). The microscopic findings of glomerular-damage (WT-1), renal tubular-damage (KIM-1), DNA-damage (γ-H2AX), inflammation (MPO/MIF/CD68) exhibited an identical pattern, whereas the podocyte components (podocin/p-cadherin/synaptopodin) displayed a reversed pattern of creatinine level (all P < 0.0001). Conclusion Combined exosome-ADMSC therapy was superior to either one for protecting kidney from acute IR injury.

KW - Acute kidney ischemia-reperfusion injury

KW - Adipose-derived mesenchymal stem cell

KW - Exosome

KW - Inflammation

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=84975321727&partnerID=8YFLogxK

U2 - 10.1016/j.ijcard.2016.04.061

DO - 10.1016/j.ijcard.2016.04.061

M3 - 文章

C2 - 27156061

AN - SCOPUS:84975321727

SN - 0167-5273

VL - 216

SP - 173

EP - 185

JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -

Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury

Abstract

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Keywords

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