Search

Purpose: 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-., Conclusion: 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.

Background: Radiation therapy is one of the most efficient treatments of neoplastic diseases used worldwide. However, patients who undergo radiotherapy may develop side effects that can be life threatening because tissue complications caused by radiation-induced stem cell depletion may result in structural and functional alterations of the surrounding matrix. This treatment also damages the osteogenic activity of human bone marrow by suppressing osteoblasts, leading to post-irradiation sequelae. Even if widely used in oncology, there is still little information on the fate and potential therapeutic efficacy of electromagnetic rays., Material and Methods: We addressed this question using both human mesenchymal stem cells and osteoblasts. Monoclonal antibody characterization identified specific surface markers for stem cells (SSEA-4, CD29, CD105, Oct 3, Nanog and SOX2) and osteoblasts (Osteopontin and Osteonectin). The technique of anti-alkaline phosphatase FITC-staining demonstrated the presence of this specific ectoenzyme. Cells were cultured in complex osteogenic medium (DMEM, 15% fetal calf serum, non-essential amino acids, L-glutamine, dexametazone, ascorbic acid, insulin, TGF-beta, BMP-2 and beta-glycero-phosphate) after being irradiated at 0.5 Gy, 1 Gy, 2 Gy and 4 Gy using a Theratron 1000 60Co source. The viability of irradiated cells was assessed using Trypan Blue staining. The comparison between cell lineages after culture in osteogenic media regarding phenotypical characterization and the intensity of the mineralization process included histology stainings (Alizarin Red S, Alcian Blue and von Kossa), and the MTT-based proliferation assay., Results: After irradiation, the proliferation and differentiation of osteoprogenitor cells is dose-dependent., Conclusions: This study is one among the first papers investigating the biophysics of low-dose gamma-irradiation on stem cell culture, focusing on the potential applications in radiation oncology and various palliative treatments.

Stem cells are undifferentiated cells that are defined by their ability to both self-renew and to differentiate in order to produce mature progeny cells, including both non-renewing progenitors and terminally differentiated effector cells. Human mesenchymal stem cells can potentially be used in therapy in a variety of conditions on the basis of their demonstrated efficiency in animal models of human diseases, varying from Parkinson's disease to neoplasia. Given that ionizing radiation is a crucial and widespread diagnostic and therapeutic tool in oncology, it is important to investigate further the factors and mechanisms that underlie stem cell radiosensitivity. The study uses human mesenchymal stem cells, characterized using monoclonal antibodies and cultured in complex osteogenic medium after being irradiated at 0.5 Gy, 1 Gy, 2 Gy and 4 Gy using a 60Co source. Genetic alterations and DNA repair were evaluated using the Alkaline comet assay. Osteogenic differentiation was confirmed by histology stainings (Alizarin Red S, Alcian Blue and von Kossa) and cell proliferation assesed using the MTT based proliferation assay. Our research team challenges current knowledge by investigating the effects of ionizing radiation on stem cells in culture, focusing on the importance of DNA damage and stem cell kinetics in oncology and radiotherapy. [ABSTRACT FROM AUTHOR]