Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation.
OBJECTIVE
Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation.


METHODS
Daily fractionated irradiation (5 × 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols.


RESULTS
Transplantation of 6 × 10(6), but not of 3 × 10(6) bone marrow stem cells on day - 1, + 4, + 8, + 11 or + 15 significantly increased the ED50 values (dose, at which an ulcer is expected in 50 % of the mice); transplantation on day + 2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day - 1, 2 or + 8 significantly, and on day + 4 marginally increased the ED50 values.


CONCLUSIONS
Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation.
Department of Radiotherapy and Radiation Oncology, OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, PF 50, 01307, Dresden, Germany, Margret.Schmidt@uniklinikum-dresden.de.
M
M
Schmidt
J
J
Haagen
R
R
Noack
A
A
Siegemund
P
P
Gabriel
W
W
Dörr
D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008809:Mice, Inbred C3H; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology / Q000601:surgery*; D013280:Stomatitis / Q000209:etiology* / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome