Characterization of the radioresponse of human apical papilla-derived cells

APDCs were isolated from freshly extracted human third molars with immature apices. Multipotent spheres, which are thought to contain an enriched population of stem/progenitor cells, were formed from the APDCs, using a neurosphere culture technique. After γ-irradiation, papillary sphere-forming cells (PSFCs) and bulk APDCs were subjected to radiosensitivity and hard tissue-forming assays.Compared to bulk APDCs, the PSFCs exhibited a radioresistant phenotype and a higher capacity for DNA double strand break repair. Irradiation induced a significant increase in a senescence-like phenotype in both cell types. Neither type of cells exhibited a significant induction of apoptotic changes after 8 Gy of irradiation. Ability to form hard tissue in vivo was significantly decreased in PSFCs, but not in APDCs following 4 Gy of irradiation.We demonstrated for the first time that stem/progenitor cells derived from APDCs exhibit a radioresistant phenotype; however, the hard tissue forming ability in vivo, but not bulk APDCs, was significantly reduced after irradiation.Since the discovery of the dental pulp stem cells (DPSCs) about 10 years ago, several studies have reported various types of DPSCs in mature permanent teeth, developing teeth, and tooth germs [1-5]. It is now a widely held view that DPSCs play a central role in forming structures of teeth [1,2]. We previously reported that apical papilla-derived cells (APDCs) derived from the tip of the apical papilla of human developing third molars with immature apices exhibit high proliferation activity and multilineage differentiation potential, and could, therefore, be an effective source of cells for hard tissue regeneration in vivo [6-8]. DPSCs are implied to originate from the cranial neural crest and differentiate not only into the mesenchymal lineage, but also into other lineages [4,6,9]. Neural crest-derived multipotent stem cells have been isolated from many tissues including the skin [10] and bone marrow [11] in rodent m