Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China.
School of Stomatology, Dalian Medical University, Liaoning, China.
Cell Prolif. 2018 Aug;51(4):e12479. doi: 10.1111/cpr.12479. Epub 2018 Jul 20.
Whole-tooth regeneration for tooth loss has long been a goal of dentistry. There is also an increasing demand to carry out pre-clinical in vitro and in vivo research methods in large animal model similar to human. The miniature pig has proven to be an alternative as a large mammal model owing to its many similarities to human. However, whole-tooth regeneration in large animal remains a challenge. Here, we investigated the feasibility of cell re-association-based whole-tooth regeneration in miniature pigs.
Single cells from the forth deciduous molar germs (p4) of pig were reconstituted to bioengineered tooth bud using different treatment for in vitro culture and in vivo transplantation in mouse subrenal capsules and jawbones.
The bioengineered tooth bud from re-aggregated epithelial to mesenchymal single cells with and without compartmentalization restored the morphogenesis, interactions or self-sorting between 2 cells in vitro culture. The pig bioengineered tooth bud transplanted in mouse subrenal capsules and jawbones restored odontogenesis and developed into large size tooth.
We characterized the morphogenesis and interaction of single-tooth germ cells in vitro, and first addressed efficient long-term survival and growth through transplantation of pig bioengineered tooth bud under mouse subrenal capsules or in mouse jawbones, where it can develop into large size tooth. Our study extends the feasibility of whole-tooth regeneration in large animal.
牙齿缺失的全牙再生一直是牙科的目标。人们也越来越要求在类似于人类的大型动物模型中进行临床前的体外和体内研究方法。小型猪已被证明是一种替代大型哺乳动物模型的方法，因为它与人有许多相似之处。然而，大型动物的全牙再生仍然是一个挑战。在这里，我们研究了在小型猪中基于细胞再聚集的全牙再生的可行性。
从小猪第四乳磨牙（p4）的单个细胞中，通过不同的处理，在体外培养和体内移植到小鼠肾包膜和颌骨中，重新构建生物工程牙芽。
来自再聚集的上皮细胞到间充质细胞的生物工程牙芽，在体外培养中恢复了形态发生、细胞间相互作用或自我分选。在小鼠肾包膜和颌骨中移植的猪生物工程牙芽恢复了牙发生，并发育成大尺寸的牙齿。
我们在体外研究了单个牙胚细胞的形态发生和相互作用，并通过在小鼠肾包膜下或小鼠颌骨中移植猪生物工程牙芽，首次解决了其长期有效存活和生长的问题，在这些部位，它可以发育成大尺寸的牙齿。我们的研究扩展了大型动物全牙再生的可行性。
