South China Center of Craniofacial Stem Cell Research, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China; Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, Pennsylvania; Research and Development Center for Tissue Engineering, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
South China Center of Craniofacial Stem Cell Research, Guanghua School and Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Endod. 2020 Sep;46(9S):S46-S55. doi: 10.1016/j.joen.2020.06.027.
Postnatal stem cells critically maintain tissue homeostasis and possess immense potential for tissue regeneration. These stem cells in the orofacial system were not identified until early 2000s when they were first found in the dental pulp and termed dental pulp stem cells (DPSCs). Isolated from either permanent or deciduous teeth, DPSCs were characterized to be highly clonogenic with multidifferentiation and neurovascular properties. Subsequent studies suggested that the origin of DPSCs may be associated with neural crest-derived cells and localized adjacent to neurovascular bundles as indicated by specific surface markers. DPSCs serve as key contributors to pulp homeostasis and injury repair. Mechanistic studies have revealed a fine-tuning regulatory network composed of both extrinsic and intrinsic factors that orchestrate fates of DPSCs. These findings have shaped our understanding of their biological nature as niche responsive progenitors. As we explore the potential of DPSCs in pulp regeneration, preclinical studies have developed diverse DPSC transplantation-based strategies, among which preconditioned DPSCs and DPSC aggregates have shown particular promise. Confirmed by recent clinical advances, DPSC transplantation after pulpectomy has successfully rebuilt the physiological pulp structure in situ functionalized with neurovascularization, indicating a novel regenerative approach for treating pulp diseases. Here, we summarized the 20-year golden journey on DPSCs from the unprecedented discovery to current clinical breakthroughs, while also suggesting future directions and challenges regarding expansion of regenerative applications and evaluation of in vivo DPSCs in diseases and therapies. The historical perspective of this field will provide a blueprint for the stem cell research and enlighten principles for de novo organ regeneration.
成体干细胞对于维持组织内稳态至关重要，具有巨大的组织再生潜力。直到 21 世纪初，人们才首次在牙髓中发现了口腔颌面系统中的这些干细胞，并将其命名为牙髓干细胞（DPSCs）。从恒牙或乳牙中分离出来的 DPSCs 具有高度克隆形成能力，并且具有多向分化和血管神经特性。随后的研究表明，DPSCs 的起源可能与神经嵴衍生细胞有关，并且定位于神经血管束附近，这可以通过特定的表面标志物来指示。DPSCs 是牙髓内稳态和损伤修复的主要贡献者。机制研究揭示了一个由外在和内在因素组成的精细调控网络，该网络协调了 DPSCs 的命运。这些发现使我们更好地理解了它们作为龛位反应性祖细胞的生物学特性。当我们探索 DPSCs 在牙髓再生中的潜力时，临床前研究已经开发了多种基于 DPSCs 移植的策略，其中预处理的 DPSCs 和 DPSCs 聚集体表现出了特别的前景。最近的临床进展证实，牙髓切除术后的 DPSCs 移植成功地在原位重建了具有血管神经化功能的生理性牙髓结构，为治疗牙髓疾病提供了一种新的再生方法。在这里，我们总结了 20 年来 DPSCs 从前所未有的发现到当前临床突破的黄金历程，同时还提出了关于再生应用扩展和体内 DPSCs 在疾病和治疗中的评估的未来方向和挑战。该领域的历史视角为干细胞研究提供了蓝图，并为从头再生器官提供了原则启示。
