Liu Ying, Gan Lu, Cui Di-Xin, Yu Si-Han, Pan Yue, Zheng Li-Wei, Wan Mian
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan Province, China.
World J Stem Cells. 2021 Nov 26;13(11):1647-1666. doi: 10.4252/wjsc.v13.i11.1647.
Regenerative endodontics (RE) therapy means physiologically replacing damaged pulp tissue and regaining functional dentin-pulp complex. Current clinical RE procedures recruit endogenous stem cells from the apical papilla, periodontal tissue, bone marrow and peripheral blood, with or without application of scaffolds and growth factors in the root canal space, resulting in cementum-like and bone-like tissue formation. Without the involvement of dental pulp stem cells (DPSCs), it is unlikely that functional pulp regeneration can be achieved, even though acceptable repair can be acquired. DPSCs, due to their specific odontogenic potential, high proliferation, neurovascular property, and easy accessibility, are considered as the most eligible cell source for dentin-pulp regeneration. The regenerative potential of DPSCs has been demonstrated by recent clinical progress. DPSC transplantation following pulpectomy has successfully reconstructed neurovascularized pulp that simulates the physiological structure of natural pulp. The self-renewal, proliferation, and odontogenic differentiation of DPSCs are under the control of a cascade of transcription factors. Over recent decades, epigenetic modulations implicating histone modifications, DNA methylation, and noncoding (nc)RNAs have manifested as a new layer of gene regulation. These modulations exhibit a profound effect on the cellular activities of DPSCs. In this review, we offer an overview about epigenetic regulation of the fate of DPSCs; in particular, on the proliferation, odontogenic differentiation, angiogenesis, and neurogenesis. We emphasize recent discoveries of epigenetic molecules that can alter DPSC status and promote pulp regeneration through manipulation over epigenetic profiles.
再生牙髓治疗（RE）是指通过生理方式替代受损的牙髓组织并恢复功能性牙本质 - 牙髓复合体。目前的临床RE程序从根尖乳头、牙周组织、骨髓和外周血中募集内源性干细胞，在根管空间中使用或不使用支架和生长因子，从而导致类牙骨质和类骨组织的形成。如果没有牙髓干细胞（DPSC）的参与，即使能够获得可接受的修复，也不太可能实现功能性牙髓再生。由于DPSC具有特定的成牙潜能、高增殖能力、神经血管特性以及易于获取，它们被认为是牙髓 - 牙本质再生最理想的细胞来源。DPSC的再生潜力已在近期的临床进展中得到证实。牙髓摘除术后进行DPSC移植已成功重建了模拟天然牙髓生理结构的神经血管化牙髓。DPSC的自我更新、增殖和成牙分化受一系列转录因子的调控。在最近几十年中，涉及组蛋白修饰、DNA甲基化和非编码（nc）RNA的表观遗传调控已成为基因调控的新层面。这些调控对DPSC的细胞活性具有深远影响。在本综述中，我们概述了DPSC命运的表观遗传调控；特别是在增殖、成牙分化、血管生成和神经发生方面。我们强调了最近发现的表观遗传分子，这些分子可以通过操纵表观遗传谱来改变DPSC的状态并促进牙髓再生。
