Published online Nov 26, 2021. doi: 10.4252/wjsc.v13.i11.1647
Peer-review started: February 28, 2021
First decision: May 5, 2021
Revised: June 7, 2021
Accepted: November 2, 2021
Article in press: November 2, 2021
Published online: November 26, 2021
Processing time: 269 Days and 19 Hours
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.
Core Tip: We review the role of epigenetic modifications during fate determination of dental pulp stem cells, highlighting cellular processes implicating proliferation, odontogenesis, angiogenesis, and neurogenesis that are tightly correlated with regenerative endodontics (RE). We emphasize the potential of epigenetic manipulation through enzyme inhibitors in RE and provide insights for future development in regaining dental pulp function.