Ionizing radiation induces senescence and differentiation of human dental pulp stem cells.

Head and neck cancer is one of the most common cancers in Europe. Many current anti-cancer treatments, including ionizing radiation, induce apoptosis via DNA damage. Unfortunately, such treatments are non-selective to cancer cells and produce similar toxicity in normal cells, including adult stem cells. One of the fundamental properties of an adult stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. However, under certain stimuli, unspecialized adult stem cells can give rise to specialized cells to generate replacements for cells that are lost during one’s life or due to injury or disease. Nevertheless, specialization of stem cells must be controlled by specific milieu and also initiated at the proper time, making the entire process beneficial for tissue recovery and maintaining it for a long time. In this paper we assess whether irradiated dental pulp stem cells have Received March 21, 2013. Accepted June 13, 2013. This study was supported by the program PRVOUK P37/01 of Charles University in Prague. R. Havelek and J. Cmielova are co-financed by the European Social Fund and the state budget of the Czech Republic. Project Nos. CZ.1.07/2.3.00/30.0058 (R.H.) and CZ.1.07/2.3.00/30.0022 (J.C.). Corresponding author: Radim Havelek, Department of Medical Biochemistry, Medical Faculty in Hradec Kralove, Simkova 870, 500 38 Hradec Kralove 1. Phone: (+420) 495 816 177; e-mail: havelekr@lfhk.cuni.cz Abbreviations: DPSCs – dental pulp stem cells, DSBs – doublestrand breaks, HNOC – head and neck/oral cancer, IR – ionizing radiation, MSCs – mesenchymal stem cells, PLSCs – periodontal ligament stem cells, RT – radiation therapy, SA-β-gal – senescence-associated β-galactosidase, SCs – stem cells, SIPS – stressinduced premature senescence. maintained open their options to mature into specialized cells, or whether they have lost their unspeciali zed (immature) state following irradiation. Our findings showed radiation-induced premature differentiation of dental pulp stem cells towards odonto-/osteoblast lineages in vitro. Matrix calcification was visualized from Day 6 or Day 9 following irradiation of cells expressing low or high levels of CD146, respectively.