title: Mesenchymal Stem Cell Therapy Protects Lungs from Radiation-Induced Endothelial Cell Loss by Restoring Superoxide Dismutase 1 Expression.
abstract: Radiation-induced normal tissue toxicity is closely linked to endothelial cell (EC) damage and dysfunction (acute effects). However, the underlying mechanisms of radiation-induced adverse late effects with respect to the vascular compartment remain elusive, and no causative radioprotective treatment is available to date.
  
  
  
  The importance of injury to EC for radiation-induced late toxicity in lungs after whole thorax irradiation (WTI) was investigated using a mouse model of radiation-induced pneumopathy. We show that WTI induces EC loss as long-term complication, which is accompanied by the development of fibrosis. Adoptive transfer of mesenchymal stem cells (MSCs) either derived from bone marrow or aorta (vascular wall-resident MSCs) in the early phase after irradiation limited the radiation-induced EC loss and fibrosis progression. Furthermore, MSC-derived culture supernatants rescued the radiation-induced reduction in viability and long-term survival of cultured lung EC. We further identified the antioxidant enzyme superoxide dismutase 1 (SOD1) as a MSC-secreted factor. Importantly, MSC treatment restored the radiation-induced reduction of SOD1 levels after WTI. A similar protective effect was achieved by using the SOD-mimetic EUK134, suggesting that MSC-derived SOD1 is involved in the protective action of MSC, presumably through paracrine signaling.
  
  
  
  In this study, we explored the therapeutic potential of MSC therapy to prevent radiation-induced EC loss (late effect) and identified the protective mechanisms of MSC action.
  
  
  
  Adoptive transfer of MSCs early after irradiation counteracts radiation-induced vascular damage and EC loss as late adverse effects. The high activity of vascular wall-derived MSCs for radioprotection may be due to their tissue-specific action. Antioxid. Redox Signal. 26, 563-582.
authors: 1 Institute of Cell Biology (Cancer Research), University Hospital, University of Duisburg-Essen , Essen, Germany .
authors: Diana
authors: D
authors: Klein
authors: 1 Institute of Cell Biology (Cancer Research), University Hospital, University of Duisburg-Essen , Essen, Germany .
authors: Jennifer
authors: J
authors: Steens
authors: 1 Institute of Cell Biology (Cancer Research), University Hospital, University of Duisburg-Essen , Essen, Germany .
authors: Alina
authors: A
authors: Wiesemann
authors: 2 Department of Chemical Biology, Faculty of Biology, Center for Medical Biotechnology, University of Duisburg-Essen , Essen, Germany .
authors: Florian
authors: F
authors: Schulz
authors: 2 Department of Chemical Biology, Faculty of Biology, Center for Medical Biotechnology, University of Duisburg-Essen , Essen, Germany .
authors: Farnusch
authors: F
authors: Kaschani
authors: 3 Institute for Pharmacology, University Hospital, Heinrich-Heine-University , Düsseldorf, Germany .
authors: Katharina
authors: K
authors: Röck
authors: 4 Department of Physiology, Kochi Medical School , Kochi, Japan .
authors: Masahiro
authors: M
authors: Yamaguchi
authors: 1 Institute of Cell Biology (Cancer Research), University Hospital, University of Duisburg-Essen , Essen, Germany .
authors: Florian
authors: F
authors: Wirsdörfer
authors: 2 Department of Chemical Biology, Faculty of Biology, Center for Medical Biotechnology, University of Duisburg-Essen , Essen, Germany .
authors: Markus
authors: M
authors: Kaiser
authors: 3 Institute for Pharmacology, University Hospital, Heinrich-Heine-University , Düsseldorf, Germany .
authors: Jens W
authors: JW
authors: Fischer
authors: 5 Department of Radiotherapy, University of Duisburg-Essen, University Hospital , Essen, Germany .
authors: Martin
authors: M
authors: Stuschke
authors: 1 Institute of Cell Biology (Cancer Research), University Hospital, University of Duisburg-Essen , Essen, Germany .
authors: Verena
authors: V
authors: Jendrossek
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005355:Fibrosis; D015870:Gene Expression; D008168:Lung / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology; D010641:Phenotype; D011832:Radiation Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011833:Radiation Injuries, Experimental; D012459:Salicylates / Q000494:pharmacology; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C433928:EUK-134; D009942:Organometallic Compounds; D012459:Salicylates; D000072105:Superoxide Dismutase-1
keywords: mesenchymal stem cell therapy; radioprotection; radiotherapy; vascular dysfunction