Induced pluripotent stem cells alleviate lung injury from mesenteric ischemia-reperfusion
| Autor: | Sen Kuang Hou, Chen-Hsen Lee, Chi Chang Juan, Shih Hwa Chiou, Cheng Ming Yang, Hsin Chin Shih, Luen Kui Chen, Hsien Hao Huang, Chorng Kuang How, Mu Shun Huang |
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| Rok vydání: | 2015 |
| Předmět: |
Pathology
medicine.medical_specialty Acute Lung Injury Blotting Western Induced Pluripotent Stem Cells Apoptosis Enzyme-Linked Immunosorbent Assay Lung injury Critical Care and Intensive Care Medicine Immunoenzyme Techniques Kruppel-Like Factor 4 Mice Random Allocation In Situ Nick-End Labeling Animals Medicine Induced pluripotent stem cell Cause of death business.industry medicine.disease Pathophysiology Mice Inbred C57BL Transplantation Mesenteric ischemia Mesenteric Ischemia Reperfusion Injury Cytokines Surgery Stem cell business Reperfusion injury |
| Zdroj: | Journal of Trauma and Acute Care Surgery. 79:592-601 |
| ISSN: | 2163-0755 |
| DOI: | 10.1097/ta.0000000000000804 |
| Popis: | 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 cell-based 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.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.The intravenously delivered iPSCs engrafted to the lungs and the ileum in response to mesenteric I/R injury. Compared with the phosphate-buffered saline-treated 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.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. |
| Databáze: | OpenAIRE |
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