Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation.

ABSTRACT

BACKGROUND AND PURPOSE: 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. MATERIAL AND 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. CONCLUSION: 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.