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springer nature additional file 1 author information authors abbreviations alp sandwich-type plla-nanosheets loaded state privacy rights cell-sheet technology l-ascorbate-2-phosphate bmc 5-μm thick sections promising cell-based therapy bone mineral content conjugated anti-human cd14 induced dpsc-sheet compared institutional ethics committee ung-il chung prevent t-cell alloreactivity 100 μm l-ascorbate-2-phosphate rights methods cell isolation tissue-engineered cell sheets small molecule bone morphogenetic protein-2 conclusions mesenchymal stem cell micro-ct images showed bone morphogenic protein author correspondence original author mesenchymal stem cells current treatment methods color-mapped images created cell-sheet engineering micro-ct image dental pulp fitc-human cd105 antibodies rt-pcr analyses showed stem cell properties total rna added achieved bone regeneration privacy choices/manage cookies induced bone regeneration convenient scaffold-free method temperature-responsive culture dishes ohba-chung laboratory osteogenic helioxanthin-derivative acts cell-based therapies sections culture methods short culture time bone mineral density

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         headline:Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology
         description:Human dental pulp stem cells (DPSCs), which have the ability to differentiate into multiple lineages, were recently identified. DPSCs can be collected readily 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 (BMSCs). Meanwhile, the treatment of severe bone defects, such as fractures, cancers, and congenital abnormalities, remains a great challenge, and novel bone regenerative techniques are highly anticipated. Several studies have previously shown that 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH), a helioxanthin derivative, induces osteogenic differentiation of preosteoblastic and mesenchymal cells. However, the osteogenic differentiation activities of TH have only been confirmed in some mouse cell lines. Therefore, in this study, toward the clinical use of TH in humans, we analyzed the effect of TH on the osteogenic differentiation of DPSCs, and the in-vivo osteogenesis ability of TH-induced DPSCs, taking advantage of the simple transplantation system using cell-sheet technology. DPSCs were obtained from dental pulp of the wisdom teeth of five healthy patients (18–22 years old) and cultured in regular medium and osteogenic medium with or without TH. To evaluate osteogenesis of TH-induced DPSCs in vivo, we transplanted DPSC sheets into mouse calvaria defects. We demonstrated that osteogenic conditions with TH induce the osteogenic differentiation of DPSCs more efficiently than those without TH and those with bone morphogenetic protein-2. However, regular medium with TH did not induce the osteogenic differentiation of DPSCs. TH induced osteogenesis in both DPSCs and BMSCs, although the gene expression pattern in DPSCs differed from that in BMSCs up to 14 days after induction with TH. Furthermore, we succeeded in bone regeneration in vivo using DPSC sheets with TH treatment, without using any scaffolds or growth factors. Our results demonstrate that TH-induced DPSCs are a useful cell source for bone regenerative medicine, and the transplantation of DPSC sheets treated with TH is a convenient scaffold-free method of bone healing.
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            Dental pulp stem cells
            Bone regeneration
            Cell-sheet technology
            Small compound
            Osteogenic differentiation
            Stem Cells
            Cell Biology
            Regenerative Medicine/Tissue Engineering
            Biomedical Engineering and Bioengineering
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      headline:Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology
      description:Human dental pulp stem cells (DPSCs), which have the ability to differentiate into multiple lineages, were recently identified. DPSCs can be collected readily 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 (BMSCs). Meanwhile, the treatment of severe bone defects, such as fractures, cancers, and congenital abnormalities, remains a great challenge, and novel bone regenerative techniques are highly anticipated. Several studies have previously shown that 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH), a helioxanthin derivative, induces osteogenic differentiation of preosteoblastic and mesenchymal cells. However, the osteogenic differentiation activities of TH have only been confirmed in some mouse cell lines. Therefore, in this study, toward the clinical use of TH in humans, we analyzed the effect of TH on the osteogenic differentiation of DPSCs, and the in-vivo osteogenesis ability of TH-induced DPSCs, taking advantage of the simple transplantation system using cell-sheet technology. DPSCs were obtained from dental pulp of the wisdom teeth of five healthy patients (18–22 years old) and cultured in regular medium and osteogenic medium with or without TH. To evaluate osteogenesis of TH-induced DPSCs in vivo, we transplanted DPSC sheets into mouse calvaria defects. We demonstrated that osteogenic conditions with TH induce the osteogenic differentiation of DPSCs more efficiently than those without TH and those with bone morphogenetic protein-2. However, regular medium with TH did not induce the osteogenic differentiation of DPSCs. TH induced osteogenesis in both DPSCs and BMSCs, although the gene expression pattern in DPSCs differed from that in BMSCs up to 14 days after induction with TH. Furthermore, we succeeded in bone regeneration in vivo using DPSC sheets with TH treatment, without using any scaffolds or growth factors. Our results demonstrate that TH-induced DPSCs are a useful cell source for bone regenerative medicine, and the transplantation of DPSC sheets treated with TH is a convenient scaffold-free method of bone healing.
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      dateModified:2018-02-01T00:00:00Z
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         Dental pulp stem cells
         Bone regeneration
         Cell-sheet technology
         Small compound
         Osteogenic differentiation
         Stem Cells
         Cell Biology
         Regenerative Medicine/Tissue Engineering
         Biomedical Engineering and Bioengineering
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      name:Department of Oral and Maxillofacial Surgery, Tokyo Medical University Hospital, Tokyo, Japan

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