title: Modification of radiation-induced oral mucositis (mouse) by adult stem cell therapy: single-dose irradiation.
abstract: Early oral mucositis occurs in response to accidental upper partial body exposure as well as to radiotherapy in the head-and-neck region. This study was initiated to define the potential of mobilization of endogenous bone marrow (BM) stem cells by rHuG-CSF or of bone marrow transplantation (BMT) to reduce the effect of single-dose irradiation on mouse oral epithelium. A 3 × 3 mm(2) area of the lower tongue surface of mice was irradiated with graded single doses (day 0). Mucosal ulceration was used as the endpoint for dose-response analyses. Stem cells were mobilized by rHuG-CSF (8 times/4 days), timed to achieve a maximum of circulating stem cells on days 0, +1, +4, +8 or +10. Alternatively, syngeneic BM was transplanted on these days. The ED(50) (dose at which ulceration is expected in 50 % of the animals) for irradiation alone was 11.9 ± 3.4 Gy. Mobilization of stem cells with a maximum of circulating stem cells on days +4, +8 or +10 significantly increased the ED(50) to 25.5 ± 10.1, 23.5 ± 10.1 and 26.5 ± 13.0 Gy. In contrast, a maximum of circulating stem cells on day 0 or day +1 had no effect. BMT did not result in a significant change in isoeffective doses in any of the protocols. In conclusion, the response of oral mucosal epithelium to a single-radiation exposure can be significantly reduced by post-exposure mobilization, but not by transplantation, of BM stem cells.
authors.affiliation: Department of Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University Dresden, 01307, Dresden, Germany, margret.schmidt@uniklinikum-dresden.de.
authors.forename: Margret
authors.initials: M
authors.lastname: Schmidt
authors.forename: Aline
authors.initials: A
authors.lastname: Piro-Hussong
authors.forename: Annett
authors.initials: A
authors.lastname: Siegemund
authors.forename: Peggy
authors.initials: P
authors.lastname: Gabriel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D016026:Bone Marrow Transplantation; D002465:Cell Movement / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D004307:Dose-Response Relationship, Radiation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology / Q000628:therapy*; D013280:Stomatitis / Q000209:etiology / Q000628:therapy*; D013997:Time Factors
chemical_list: D016179:Granulocyte Colony-Stimulating Factor