Journal Article

SHED aggregate exosomes shuttled miR‐26a promote angiogenesis in pulp regeneration via TGF‐β/SMAD2/3 signalling

Wu, Meiling, Guo, Hao, Liu, Xuemei, Guo, Xiaohe, Jin, Yan, Yang, Xiaoxue, Li, Bei, Li, Zihan, Xuan, Kun, Huang, Xiaoyao

2021

Overview

Objectives Pulp regeneration brings big challenges for clinicians, and vascularization is considered as its determining factor. We previously accomplished pulp regeneration with autologous stem cells from deciduous teeth (SHED) aggregates implantation in teenager patients, however, the underlying mechanism needs to be clarified for regenerating pulp in adults. Serving as an important effector of mesenchymal stem cells (MSCs), exosomes have been reported to promote angiogenesis and tissue regeneration effectively. Here, we aimed to investigate the role of SHED aggregate‐derived exosomes (SA‐Exo) in the angiogenesis of pulp regeneration. Materials and Methods We extracted exosomes from SHED aggregates and utilized them in the pulp regeneration animal model. The pro‐angiogenetic effects of SA‐Exo on SHED and human umbilical vein endothelial cells (HUVECs) were evaluated. The related mechanisms were further investigated. Results We firstly found that SA‐Exo significantly improved pulp tissue regeneration and angiogenesis in vivo. Next, we found that SA‐Exo promoted SHED endothelial differentiation and enhanced the angiogenic ability of HUVECs, as indicated by the in vitro tube formation assay. Mechanistically, miR‐26a, which is enriched in SA‐Exo, improved angiogenesis both in SHED and HUVECs via regulating TGF‐β/SMAD2/3 signalling. Conclusions In summary, these data reveal that SA‐Exo shuttled miR‐26a promotes angiogenesis via TGF‐β/SMAD2/3 signalling contributing to SHED aggregate‐based pulp tissue regeneration. These novel insights into SA‐Exo may facilitate the development of new strategies for pulp regeneration. The underlying mechanisms of the SHED aggregate involved in pulp regeneration is revealed in this paper. SHED aggregate‐derived exosomes (SA‐Exo) shuttled miR‐26a promote SHED endothelial differentiation and enhance the angiogenic ability of HUVECs via TGF‐β/SMAD2/3 signalling, which contributing to angiogenesis in pulp tissue regeneration.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Aggregates / Angiogenesis / Aniline Compounds - pharmacology / Animal models / Antagomirs - metabolism / Antibodies / Autografts / Benzylidene Compounds - pharmacology / Cell Differentiation - drug effects / Dental pulp / Dental Pulp - physiology / Effector cells / Endodontics / Endothelial cells / exosome / Exosomes / Exosomes - metabolism / Exosomes - transplantation / Human Umbilical Vein Endothelial Cells / Humans / Laboratory animals / Mesenchyme / MicroRNAs - antagonists & inhibitors / MicroRNAs - genetics / MicroRNAs - metabolism / miR‐26a / Neovascularization, Physiologic - drug effects / Original / pulp regeneration / Regeneration / Regeneration - drug effects / SHED aggregate / Signal Transduction - drug effects / Signaling / Smad2 protein / Smad2 Protein - metabolism / Smad3 Protein - metabolism / Stem cell transplantation / Stem cells / Stem Cells - cytology / Stem Cells - metabolism / Teeth / TGF‐β signalling / Tissue engineering / Tooth, Deciduous - cytology / Transforming Growth Factor beta - metabolism / Transforming growth factor-b / Umbilical vein / Vascularization