Abstract
Introduction
Regenerative endodontics has created a desirable shift in the treatment paradigm despite
current limitations of regenerative outcomes. Mesenchymal stem cells (MSCs) facilitate
tissue regeneration and repair in a mild inflammatory environment. Small extracellular
vesicles (sEVs) derived from MSCs play an imperative role in the paracrine modulation
of regenerative responses modulated by MSCs. However, it remains unknown whether MSCs
enhance dental pulp regeneration or whether this enhancement is mediated by sEVs in
a mild inflammatory environment. The present study aimed to elucidate the effects
of sEVs originated from lipopolysaccharide (LPS)-preconditioned human dental pulp
stem cells (hDPSCs) on dental pulp regeneration.
Methods
All sEVs were isolated from hDPSCs cultured with or without LPS (ie, N-sEVs and L-sEVs,
respectively). The effect of N-sEVs and L-sEVs on proliferation, migration, angiogenesis,
and differentiation of rat bone marrow MSCs was identified in vitro. Moreover, N-sEVs or L-sEVs were implanted into rat pulpless root canal models, and
the regenerated tissue in root canals was assessed via hematoxylin-eosin staining,
Masson staining, and immunohistochemistry after 30 days of transplantation.
Results
Both N-sEVs and L-sEVs could modulate BMSC proliferation, migration, angiogenesis,
and differentiation. Both kinds of sEVs enhanced the structure of the regenerated
tissue closer to that of a normal dental pulp in vivo. L-sEVs had a more significant effect than N-sEVs.
Conclusions
sEVs released by hDPSCs in a mild inflammatory microenvironment are capable of facilitating
the regeneration of dental pulp through functional healing instead of scar healing,
which has potential applications in regenerative endodontics.
Key Words
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Article info
Publication history
Published online: March 25, 2021
Identification
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© 2021 American Association of Endodontists.
