A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue.
A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue.
复制标题
DOI：
10.1089/ten.tec.2017.0342
复制
发表时间：
2018-02
期刊：
影响因子：
--
通讯作者：
Xiaofei Zhu;Jie Liu;Zongdong Yu;Chao-An Chen;H. Aksel;Adham A. Azim;G. T. Huang
中科院分区：
文献类型：
--
作者：
Xiaofei Zhu;Jie Liu;Zongdong Yu;Chao-An Chen;H. Aksel;Adham A. Azim;G. T. Huang
本研究的目的是建立小型猪作为大型动物模型的干细胞为基础的牙髓再生研究。从小型猪中分离猪牙髓干细胞（sDPSC）并进行体外鉴定。对于体内研究，我们首先采用异位和半原位研究模型，使用严重的联合免疫缺陷小鼠。一种是羟基磷灰石-磷酸三钙（HA/TCP）模型，用于牙髓-牙本质复合体的形成;另一种是牙体碎片模型，用于牙髓再生，新牙本质沿着管壁沉积。我们发现sDPSCs与人类的同类细胞相似，表现出间充质干细胞的特性，具有形成集落形成单位-成纤维细胞和牙源性分化潜能的能力。sDPSCs在HA/TCP模型中形成牙髓-牙本质复合体，在牙体碎片模型中显示牙髓再生能力。然后，我们测试了原位牙髓再生小型猪，包括使用多根牙。将自体sDPSCs通过水凝胶载体移植到小型猪根管内，我们观察到血管化牙髓样组织再生，并沿管壁有一层新沉积的牙本质样（rD）组织或骨牙本质沿着生长。部分病例可见牙本质桥样结构。免疫组化检测nestin、牙本质涎磷蛋白、牙本质基质蛋白1和骨涎蛋白在成牙本质细胞样细胞中的表达。我们还测试了同种异体sDPSC在相同程序中的使用。在同种异体移植中也观察到类似的结果。这项研究是第一次显示，建立小型猪作为一个合适的大型动物模型，利用多根牙齿进一步细胞为基础的牙髓再生研究。
The goal of this study was to establish mini-swine as a large animal model for stem cell-based pulp regeneration studies. Swine dental pulp stem cells (sDPSCs) were isolated from mini-swine and characterized in vitro. For in vivo studies, we first employed both ectopic and semi-orthotopic study models using severe combined immunodeficiency mice. One is hydroxyapatite-tricalcium phosphate (HA/TCP) model for pulp-dentin complex formation, and the other is tooth fragment model for complete pulp regeneration with new dentin depositing along the canal walls. We found that sDPSCs are similar to their human counterparts exhibiting mesenchymal stem cell characteristics with ability to form colony forming unit-fibroblastic and odontogenic differentiation potential. sDPSCs formed pulp-dentin complex in the HA/TCP model and showed pulp regeneration capacity in the tooth fragment model. We then tested orthotopic pulp regeneration on mini-swine including the use of multi-rooted teeth. Using autologous sDPSCs carried by hydrogel and transplanted into the mini-swine root canal space, we observed regeneration of vascularized pulp-like tissue with a layer of newly deposited dentin-like (rD) tissue or osteodentin along the canal walls. In some cases, dentin bridge-like structure was observed. Immunohistochemical analysis detected the expression of nestin, dentin sialophosphoprotein, dentin matrix protein 1, and bone sialoprotein in odontoblast-like cells lining against the produced rD. We also tested the use of allogeneic sDPSCs for the same procedures. Similar findings were observed in allogeneic transplantation. This study is the first to show an establishment of mini-swine as a suitable large animal model utilizing multi-rooted teeth for further cell-based pulp regeneration studies.