title: Bone Marrow-derived Cell Therapy for Oral Mucosal Repair after Irradiation.
abstract: Oral mucositis (ulcer) is a serious and painful side effect for patients with head and neck cancer following radiation therapy. However, current clinical strategies cannot efficiently prevent the occurrence of oral mucositis. In this study, we investigated whether bone marrow-derived cells (BMDCs) prevented the occurrence and/or decreased the severity of radiation-induced oral mucositis. Fresh concentrated BMDCs from male C3H mice were transplanted intravenously into female mice after tongue irradiation. For 14 days postirradiation, the changes of body weight and the time courses of ulceration were observed. Until the ulcer reached maximum size (7 days postirradiation), macroscopic and histologic analyses of harvested tongues were performed to detect the behavior of donor BMDCs. Between 2 and 5 days postirradiation, BMDCs-transplanted mice showed more expression of stem cell markers (c-Kit, Sca-1) and EGFR and fewer apoptotic cells when compared with nontransplanted control mice (irradiation group). On day 7, there were fewer and smaller ulcers observed in the BMDCs-transplanted group. Tongues of these mice had preserved their epithelial thickness, and regenerative activities (blood vessels formation, cell proliferation) were higher than they were in the irradiation group. Fluorescently labeled BMDCs were not detected in tongue epithelium but rather in connective tissue (dermis) just below the basal cell layer. These findings suggest that exogenous BMDCs behave to reduce radiogenic oral mucositis in a paracrine manner.
authors: Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: T
authors: T
authors: I
authors: Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan y-sumita@nagasaki-u.ac.jp.
authors: Y
authors: Y
authors: Sumita
authors: Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: T
authors: T
authors: Minamizato
authors: Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: M
authors: M
authors: Umebayashi
authors: Laboratory of Craniofacial Tissue Engineering, Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
authors: Y
authors: Y
authors: Liu
authors: Laboratory of Craniofacial Tissue Engineering, Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
authors: S D
authors: SD
authors: Tran
authors: Department of Regenerative Oral Surgery, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: I
authors: I
authors: Asahina
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001485:Basement Membrane / Q000473:pathology / Q000528:radiation effects; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology / Q000528:radiation effects; D005260:Female; D005928:Glossitis / Q000209:etiology / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018919:Neovascularization, Physiologic / Q000502:physiology; D019226:Oral Ulcer / Q000209:etiology / Q000628:therapy; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011832:Radiation Injuries / Q000628:therapy*; D011897:Random Allocation; D062326:Re-Epithelialization / Q000502:physiology; D012038:Regeneration / Q000502:physiology; D014059:Tongue / Q000473:pathology / Q000528:radiation effects*
chemical_list: D018809:Proliferating Cell Nuclear Antigen
keywords: cell transplantaion; epithelial tissue; mucosal regeneration; paracrine effect; radiation injury; stem cells