Mesenchymal stem cell irradiation in culture engages differential effect of hyper-fractionated radiotherapy for head and neck cancers.
OBJECTIVE
The purpose of this study was to challenge current knowledge on the potential therapeutic advantages of stem cells in radiotherapy by developing an in vitro model of the healthy tissue surrounding or replacing the widely resected tumor. After radical surgery, the start of radiotherapy is often delayed due to wound healing process, with potential loss of the opportunity for treating microscopic disease instead of macroscopic early recurrence. Hyperfractionated radiotherapy, contrary to the standard one, can extend the limits of radical surgery and shorten the gap before the onset of postoperative radiotherapy, with potential improvement in local control.


METHODS
By using both mesenchymal stem cells and pre-differentiated osteoblasts, cultured in proper pro-osteogenic media after cell irradiation, we investigated both the differences in the response to DNA damage between lineages undergoing differentiation in culture and the intensity of the mineralization process.


RESULTS
Ionizing radiation stimulated stem cell proliferation and differentiation at 0.5 Gy and 1 Gy, thus confirming in vitro the clinical results of hyperfractionated irradiation randomized trials in head and neck cancers -HNCs-.


CONCLUSIONS
To our knowledge, this study is the first to investigate the biophysics of low dose gamma irradiation on stem cell culture, focusing on the potential applications in radiation oncology. For advanced oral cavity and oropharyngeal cancers, as radical surgery often implies major bone resection, the use of mesenchymal stem cells as bone reconstruction vectors might shorten the onset of adjuvant hyperfractionated radiotherapy which enhances the mineralization process. As postoperative radiotherapy has recently being revisited for osteosarcoma, this scenario could impact also on bone reconstruction process in this pathology.
Tomuleasa
C
C
Laboratory of Experimental Radiotherapy and Stem Cell Culture, Ion Chiricuta Comprehensive Cancer Center, Cluj-Napoca, Romania. ciprian.tomuleasa@gmail.com
Soritau
O
O
Brie
I
I
Pall
E
E
Foris
V
V
Dicu
T
T
Virag
P
P
Irimie
A
A
Kacso
G
G
D018929:Cell Culture Techniques; D002455:Cell Division; D002469:Cell Separation; D003037:Cobalt Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000528:radiation effects*; D010006:Osteoblasts / Q000528:radiation effects; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods
D003037:Cobalt Radioisotopes