Stem/Progenitor Cell-Mediated De Novo Regeneration of Dental Pulp with Newly Deposited Continuous Layer of Dentin in an In Vivo Model
Stem/Progenitor Cell-Mediated De Novo Regeneration of Dental Pulp with Newly Deposited Continuous Layer of Dentin in an In Vivo Model
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DOI：
10.1089/ten.tea.2009.0518
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发表时间：
2010-02-01
影响因子：
4.1
通讯作者：
Shi, Songtao
中科院分区：
文献类型：
--
作者：
Huang, George T. -J.;Yamaza, Takayoshi;Shi, Songtao
本研究的最终目标是通过干细胞/祖细胞为基础的方法和组织工程技术来再生失去的牙髓和牙本质。在这项研究中，我们使用干细胞/祖细胞介导的方法，利用人牙根碎片和免疫功能受损的小鼠模型，测试了在清空的根管空间中再生血管化的人牙髓和在现有牙管壁上产生新牙本质的可能性。从根尖乳头和牙髓干细胞中分离出干细胞/祖细胞，对其进行鉴定，将其植入由聚d、l -丙交酯/乙醇酸酯组成的合成支架中，插入牙齿碎片中，移植到小鼠体内。我们的结果显示，根管空间完全被具有良好血管的髓样组织填充。此外，一层连续的牙本质样组织沉积在根管牙本质壁上。这种牙本质样结构似乎是由一层新形成的成牙细胞样细胞产生的，这些细胞表达牙本质唾液蛋白、骨唾液蛋白、碱性磷酸酶和CD105。再生浆样组织中的细胞对抗人线粒体抗体反应积极，表明它们来自人类。本研究首次证明了牙髓样组织可以在清空的根管空间中由来自根尖乳头和牙髓干细胞的干细胞重新再生，牙髓干细胞产生成牙细胞样细胞，在现有的牙本质壁上产生牙本质样组织。
The ultimate goal of this study is to regenerate lost dental pulp and dentin via stem/progenitor cell-based approaches and tissue engineering technologies. In this study, we tested the possibility of regenerating vascularized human dental pulp in emptied root canal space and producing new dentin on existing dentinal walls using a stem/progenitor cell-mediated approach with a human root fragment and an immunocompromised mouse model. Stem/progenitor cells from apical papilla and dental pulp stem cells were isolated, characterized, seeded onto synthetic scaffolds consisting of poly-D, L-lactide/glycolide, inserted into the tooth fragments, and transplanted into mice. Our results showed that the root canal space was filled entirely by a pulp-like tissue with well-established vascularity. In addition, a continuous layer of dentin-like tissue was deposited onto the canal dentinal wall. This dentin-like structure appeared to be produced by a layer of newly formed odontoblast-like cells expressing dentin sialophosphoprotein, bone sialoprotein, alkaline phosphatase, and CD105. The cells in regenerated pulp-like tissue reacted positively to anti-human mitochondria antibodies, indicating their human origin. This study provides the first evidence showing that pulp-like tissue can be regenerated de novo in emptied root canal space by stem cells from apical papilla and dental pulp stem cells that give rise to odontoblast-like cells producing dentin-like tissue on existing dentinal walls.