Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion

Chorng Kuang How, Sen Kuang Hou, Luen Kui Chen, Cheng Ming Yang, Hsien Hao Huang, Hsin Chin Shih, Mu Shun Huang, Shih Hwa Chiou, Chen Hsen Lee, Chi Chang Juan

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)592-601
Number of pages10
JournalJournal of Trauma and Acute Care Surgery
Volume79
Issue number4
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Keywords

  • Induced pluripotent stem cells
  • Lung injury
  • Mesenteric ischemia-reperfusion
  • Mice
  • Transplantation

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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  • Cite this

    How, C. K., Hou, S. K., Chen, L. K., Yang, C. M., Huang, H. H., Shih, H. C., Huang, M. S., Chiou, S. H., Lee, C. H., & Juan, C. C. (2015). Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion. Journal of Trauma and Acute Care Surgery, 79(4), 592-601. https://doi.org/10.1097/TA.0000000000000804