Bone regeneration potential of human dental pulp stem cells derived from elderly patients and induced by a helioxanthin derivative

<title>Abstract</title> <p><bold>Background:</bold> Human dental pulp stem cells (DPSCs) have the ability to differentiate into multiple lineage cell types including adipogenic, neurogenic, and osteogenic cells. Dental pulp stem cells can be easily collected from extracted teeth and are now considered to be a type of mesenchymal stem cell with higher clonogenic and proliferative potential than bone marrow stem cells. Previous studies have described the osteogenic ability of DPSCs that were isolated from only young patients. However, in fact, elderly patients more frequently require bone regenerative therapy—for example, in alveolar bone defects resulting from periodontal disease—than young patients. We previously reported that 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH), a helioxanthin derivative, induces osteogenic differentiation of DPSCs derived from young patients. However, the effect of TH on the osteogenic differentiation potential of DPSCs derived from elderly patients remains unknown. Therefore, the present study aimed to examine and compare the osteogenic differentiation potential of TH-induced DPSCs from elderly patients and young patients to explore the potential clinical use of DPSCs for elderly patients.<bold>Methods: </bold>Dental pulp stem cells were obtained from the dental pulp of teeth of healthy young patients (18-39 years old) and healthy elderly patients (40-67 years old) and cultured in regular medium and osteogenic medium with or without TH. We assessed the morphological characteristics, proliferation, and osteogenic differentiation of DPSCs from both young and elderly patients. Moreover, DPSC sheets were transplanted into mouse calvarial defects to investigate osteogenesis of TH-induced DPSCs <italic>in vivo.</italic><bold>Results: </bold>We demonstrated that osteogenic conditions with TH induce the osteogenic differentiation and osteogenesis of DPSCs from elderly patients as well as young patients more than osteogenic conditions without TH. <bold>Conclusions: </bold>Our results suggested that the osteogenic differentiation potential of DPSCs from elderly patients is as high as that of DPSCs from young patients. Moreover, TH-induced DPSCs show increased osteogenic differentiation potential, and they can be a useful cell source for bone regenerative therapy for not only young patients but also elderly patients.</p>