Odontogenesis-related developmental microenvironment facilitates deciduous dental pulp stem cell aggregates to revitalize an avulsed tooth
Odontogenesis-related developmental microenvironment facilitates deciduous dental pulp stem cell aggregates to revitalize an avulsed tooth
复制标题
成牙相关的发育微环境有利于乳牙髓干细胞聚集，使撕脱牙恢复活力。
DOI：
10.1016/j.biomaterials.2021.121223
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发表时间：
2021-11-01
期刊：
影响因子：
14
通讯作者：
Jin, Yan
中科院分区：
文献类型：
--
作者：
Guo, Hao;Li, Bei;Jin, Yan
利用组织工程的发展过程是再生医学的一种前景看好但具有挑战性的方法。牙齿撕脱是最严重的创伤性牙齿损伤之一，而牙齿再生的功能仍不确定。在这里，我们建立了一种策略，使用脱细胞牙齿基质(DTM)和人牙髓干细胞(HDPSC)聚集体来模拟与牙齿发生相关的发育微环境。以此方法重建的生物工程牙植入牙槽骨后，在临床前猪模型中再生具有血管和神经的三维牙髓和牙周组织。这些结果促使我们招募了15名外伤性牙齿损伤后撕脱牙齿的患者参加一项试点临床试验。在植入12个月后，生物工程牙齿导致了功能牙齿的再生，这支持了人类牙根的持续发育。从机制上讲，hDPSC聚集体衍生的外切体通过上调hDPSC的成牙能力和血管生成能力来介导牙齿再生过程。我们的研究结果表明，DTM和干细胞聚集体的牙源性微环境工程启动了功能性牙齿再生，是治疗牙齿撕脱的一种有效方法。
Harnessing developmental processes for tissue engineering represents a promising yet challenging approach to regenerative medicine. Tooth avulsion is among the most serious traumatic dental injuries, whereas functional tooth regeneration remains uncertain. Here, we established a strategy using decellularized tooth matrix (DTM) combined with human dental pulp stem cell (hDPSC) aggregates to simulate an odontogenesis-related developmental microenvironment. The bioengineered teeth reconstructed by this strategy regenerated threedimensional pulp and periodontal tissues equipped with vasculature and innervation in a preclinical pig model after implantation into the alveolar bone. These results prompted us to enroll 15 patients with avulsed teeth after traumatic dental injuries in a pilot clinical trial. At 12 months after implantation, bioengineered teeth led to the regeneration of functional teeth, which supported continued root development, in humans. Mechanistically, exosomes derived from hDPSC aggregates mediated the tooth regeneration process by upregulating the odontogenic and angiogenic ability of hDPSCs. Our findings suggest that odontogenic microenvironment engineering by DTM and stem cell aggregates initiates functional tooth regeneration and serves as an effective treatment for tooth avulsion.