Bone Marrow-derived Cell Therapy for Oral Mucosal Repair after Irradiation.
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.
['I|T|T|', 'Sumita|Y|Y|', 'Minamizato|T|T|', 'Umebayashi|M|M|', 'Liu|Y|Y|', 'Tran|S D|SD|', 'Asahina|I|I|']
D000818:Animals D017209:Apoptosis D001485:Basement Membrane D016026:Bone Marrow Transplantation D004195:Disease Models, Animal D004848:Epithelium D005260:Female D005928:Glossitis D008297:Male D051379:Mice D008809:Mice, Inbred C3H D018919:Neovascularization, Physiologic D019226:Oral Ulcer D018809:Proliferating Cell Nuclear Antigen D011832:Radiation Injuries D011897:Random Allocation D062326:Re-Epithelialization D012038:Regeneration D014059:Tongue
stem cells cell transplantaion epithelial tissue mucosal regeneration paracrine effect radiation injury