TY - JOUR
T1 - Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion
AU - How, Chorng Kuang
AU - Hou, Sen Kuang
AU - Chen, Luen Kui
AU - Yang, Cheng Ming
AU - Huang, Hsien Hao
AU - Shih, Hsin Chin
AU - Huang, Mu Shun
AU - Chiou, Shih Hwa
AU - Lee, Chen Hsen
AU - Juan, Chi Chang
N1 - Publisher Copyright:
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015
Y1 - 2015
N2 - BACKGROUND: Mesenteric ischemia-reperfusion (I/R) injury is a serious pathophysiologic process that can trigger the development of multiorgan dysfunction. Acute lung injury is a major cause of death among mesenteric I/R patients, as current treatments remain inadequate. Stem cellYbased therapies are considered novel strategies for treating several devastating and incurable diseases. This study examined whether induced pluripotent stem cells (iPSCs) lacking c-myc (i.e., induced using only the three genes oct4, sox2, and klf4) can protect against acute lung injury in a mesenteric I/R mouse model. METHODS: C57BL/6 mice were randomly divided into the following groups: sham/no treatment, vehicle treatment with phosphate-buffered saline, treatment with iPSCs, and treatment with iPSC-conditioned medium. The mice were subjected to mesenteric ischemia for 45 minutes followed by reperfusion for 24 hours. After I/R, the lungs and the ileum of the mice were harvested. Lung injury was evaluated by histology, immunohistochemistry, and analyses of the levels of inflammatory cytokines, cleaved caspase 3, and 4-hydroxynonenal. RESULTS: The intravenously delivered iPSCs engrafted to the lungs and the ileum in response to mesenteric I/R injury. Compared with the phosphate-buffered salineYtreated group, the iPSC-treated group displayed a decreased intensity of acute lung injury 24 hours after mesenteric I/R. iPSC transplantation significantly reduced the expression of proinflammatory cytokines, oxidative stress markers, and apoptotic factors in injured lung tissue and remarkably enhanced endogenous alveolar cell proliferation. iPSC-conditioned medium treatment exerted a partial effect compared with iPSC treatment. CONCLUSION: When considering the anti-inflammatory, antioxidant, and antiapoptotic properties of iPSCs, the transplantation of iPSCs may represent an effective treatment option for mesenteric I/R-induced acute lung injury.
AB - BACKGROUND: Mesenteric ischemia-reperfusion (I/R) injury is a serious pathophysiologic process that can trigger the development of multiorgan dysfunction. Acute lung injury is a major cause of death among mesenteric I/R patients, as current treatments remain inadequate. Stem cellYbased therapies are considered novel strategies for treating several devastating and incurable diseases. This study examined whether induced pluripotent stem cells (iPSCs) lacking c-myc (i.e., induced using only the three genes oct4, sox2, and klf4) can protect against acute lung injury in a mesenteric I/R mouse model. METHODS: C57BL/6 mice were randomly divided into the following groups: sham/no treatment, vehicle treatment with phosphate-buffered saline, treatment with iPSCs, and treatment with iPSC-conditioned medium. The mice were subjected to mesenteric ischemia for 45 minutes followed by reperfusion for 24 hours. After I/R, the lungs and the ileum of the mice were harvested. Lung injury was evaluated by histology, immunohistochemistry, and analyses of the levels of inflammatory cytokines, cleaved caspase 3, and 4-hydroxynonenal. RESULTS: The intravenously delivered iPSCs engrafted to the lungs and the ileum in response to mesenteric I/R injury. Compared with the phosphate-buffered salineYtreated group, the iPSC-treated group displayed a decreased intensity of acute lung injury 24 hours after mesenteric I/R. iPSC transplantation significantly reduced the expression of proinflammatory cytokines, oxidative stress markers, and apoptotic factors in injured lung tissue and remarkably enhanced endogenous alveolar cell proliferation. iPSC-conditioned medium treatment exerted a partial effect compared with iPSC treatment. CONCLUSION: When considering the anti-inflammatory, antioxidant, and antiapoptotic properties of iPSCs, the transplantation of iPSCs may represent an effective treatment option for mesenteric I/R-induced acute lung injury.
KW - Induced pluripotent stem cells
KW - Lung injury
KW - Mesenteric ischemia-reperfusion
KW - Mice
KW - Transplantation
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U2 - 10.1097/TA.0000000000000804
DO - 10.1097/TA.0000000000000804
M3 - Article
C2 - 26402533
AN - SCOPUS:84942598166
SN - 2163-0755
VL - 79
SP - 592
EP - 601
JO - Journal of Trauma and Acute Care Surgery
JF - Journal of Trauma and Acute Care Surgery
IS - 4
ER -