Abstract
Human dental pulp stem cells (DPSCs) have high clonogenic and proliferative potential. We previously reported that a helioxanthin derivative (4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2–b]pyridine-2-carboxamide (TH)) enhances osteogenic differentiation of DPSCs derived from young patients. However, in the clinical field, elderly patients more frequently require bone regenerative therapy than young patients. In this study, we examined and compared 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. DPSCs were obtained from young and elderly patients and cultured in osteogenic medium with or without TH. We assessed the characteristics and osteogenic differentiation by means of specific staining and gene expression analyses. Moreover, DPSC sheets were transplanted into mouse calvarial defects to investigate osteogenesis of TH-induced DPSCs by performing micro-computed tomography (micro-CT). We demonstrated that osteogenic conditions with TH enhance the osteogenic differentiation marker of DPSCs from elderly patients as well as young patients in vitro. In vivo examination showed increased osteogenesis of DPSCs treated with TH from both elderly patients and young patients. Our results suggest that the osteogenic differentiation potential of DPSCs from elderly patients is as high as that of DPSCs from young patients. Moreover, TH-induced DPSCs showed increased osteogenic differentiation potential, and are thus a potentially useful cell source for bone regenerative therapy for elderly patients.
Highlights
Bone regenerative therapy is in great demand nowadays for alveolar bone loss caused by periodontitis, tumor resection, traumatic injury, and dental implant therapy
In P2, the proliferation potential of elderly dental pulp stem cells (DPSCs) increased and was not significantly different from that of young DPSCs—it remained at a high level in passage 3 (P3) (Figure 1b)
To assess whether TH can be used in DPSCs derived from elderly patients, we examined the effect of TH on the osteogenic differentiation potential of DPSCs from elderly patients in a mouse calvarial defect model and compared it with that of DPSCs from young patients
Summary
Bone regenerative therapy is in great demand nowadays for alveolar bone loss caused by periodontitis, tumor resection, traumatic injury, and dental implant therapy. Bone augmentation techniques such as bone harvesting from the iliac crest under general anesthesia, autogenous bone grafting from the mandible, and artificial bone grafting have been used for alveolar bone defect in periodontitis treatment and dental implant treatment These present a high likelihood of infection and unexpected resorption. We showed that 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2–b]pyridine-2-carboxamide (TH)—a small-molecule derivative of helioxanthin—induces osteogenic differentiation of DPSCs isolated from young patients in vitro and in vivo, using transplantation of DPSCs with cell sheet technology [18].
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