Background: Mesenchymal stem cells (MSCs) in teeth have been exploited as vital seed
cells for stem cell-based dental medicine. To date, several mesenchymal stem cell populations originated
from odontogenic tissue have been isolated and characterized by their expression of MSC surface
markers and capacity of multi-lineage differentiation, including dental pulp stem cells (DPSCs), stem
cells from human exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP) and so on.
However, their identity in vivo remains elusive, which hinders further understanding of their application
in stem cell-based tooth regeneration. Label retaining and lineage tracing analyses, which serve as
gold standards for identification of stem cells in vivo, provide feasibility for identifying MSCs in teeth.
Objectives: In this review, we will discuss the issues of MSCs, including the origin and identification
of both odontogenic and non-odontogenic MSCs, and address the role of nerve-derived Sonic hedgehog
(Shh) in the regulation of MSCs in the neurovascular bundle (NVB).
Conclusion: Based on label retaining and lineage tracing analyses, latest studies have found new populations
of non-odontogenic MSCs in teeth, periarterial-derived and glial-derived, regulated by the Shh
derived from nerves in the NVB, which provides a new hope for tooth regeneration.