title: Tissue-engineered oral mucosa to study radiotherapy-induced oral mucositis.
abstract: OBJECTIVE
  Oral mucositis is a severe and often dose-limiting side-effect of cancer therapy that occurs in patients receiving radiotherapy for head and neck cancers. Although radiation-induced effects on keratinocytes have been studied, little is known about its effect on fibroblasts or endothelial cells or, more importantly, when all these cells are combined in an engineered oral mucosal model.
  
  
  METHODS
  Monolayer cultures of normal oral keratinocytes, normal oral fibroblasts, human dermal microvascular endothelial cells or tissue-engineered oral mucosa (TEOM) were exposed to 20 Gy irradiation. Cell damage and cytokine release was measured for 72 h for monolayer cultures and for up to 21 d for TEOM.
  
  
  RESULTS
  Compared to non-irradiated cells, the viability of all monolayer and co-cultures was significantly reduced 72 h post-irradiation while levels of secreted interleukin IL-6 and CXCL8 were increased. The viability of irradiated TEOM models was significantly reduced compared to controls at all time-points. Histologically, irradiated TEOM displayed thinner epithelium, increased apoptosis and more extensive damage than non-irradiated models. IL-6, CXCL8 and granulocyte macrophage colony-stimulating factor release was reduced whereas IL-1α levels were increased in irradiated TEOM models compared to controls.
  
  
  CONCLUSIONS
  TEOM models comprising of mixed cell populations may prove useful in examining the pathobiology of radiation-induced mucositis.
authors.affiliation: Academic Unit of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, University of Sheffield , Sheffield , UK.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Colley
authors.forename: Paula C
authors.initials: PC
authors.lastname: Eves
authors.forename: Abigail
authors.initials: A
authors.lastname: Pinnock
authors.forename: Martin H
authors.initials: MH
authors.lastname: Thornhill
authors.forename: Craig
authors.initials: C
authors.lastname: Murdoch
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D009061:Mouth Mucosa / Q000473:pathology / Q000528:radiation effects*; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology*; D011878:Radiotherapy / Q000009:adverse effects*; D013280:Stomatitis / Q000209:etiology* / Q000473:pathology*; D023822:Tissue Engineering
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8