SHED promote angiogenesis in stem cell-mediated dental pulp regeneration

Guo, Hao; Zhao, Wei; Liu, Anqi; Wu, Ming-Hsien; Yi, Siyan; Li, Bei; Huang, Xiaoguang; Liu, Xuemei; Yang, Xiaoxue; Guo, Xiang; Xuan, Kun; Jin, Yan

doi:10.1016/j.bbrc.2020.06.151

Cited by 37 publications

(33 citation statements)

References 27 publications

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“…All included studies except for one [ 27 ] used large animal models for orthotopic de novo pulp regeneration [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 29 , 30 , 31 , 33 , 34 ]. A dog model (73%) [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 29 , 30 ] was found to be the most common, followed by a pig model (20%) [ 31 , 33 , 34 ]. A rat model was used in one study [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

“…Molars were used in a small animal model [ 27 ]. Twelve studies used incisors [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 31 , 33 ], while three studies used premolars [ 29 , 30 , 31 ]. One study used both incisors and premolars in a large animal model [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…Other mesenchymal stem cells such as bone marrow stem cells (BMSC) [26,28], adipose-derived stem cells (ADSC) [20,26,28], and stem have been most widely used to regenerate the pulp-dentin complex [19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Other mesenchymal stem cells such as bone marrow stem cells (BMSC) [26,28], adipose-derived stem cells (ADSC) [20,26,28], and stem cells from human exfoliated deciduous teeth (SHED) [33,34] have also been tested for dental pulp regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…There have been increasing attempts to regenerate the pulp–dentin complex by transplanting mesenchymal stem cells in animal studies [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 33 , 34 ] and clinical trials [ 32 , 34 ]. The aim of this study was to systematically review the performance of various types of mesenchymal stem cells for dental pulp regeneration and their tissue engineering protocols for clinical translation and applicability.…”

Section: Introductionmentioning

confidence: 99%

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A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review

Kim

2021

IJMS

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Despite the recent explosion of investigations on dental pulp regeneration using various tissue engineering strategies, the translation of the findings from such studies into therapeutic applications has not been properly achieved. The purpose of this scoping review was to systematically review the efficacy of mesenchymal stem cell transplantation for dental pulp regeneration. A literature search was conducted using five electronic databases from their inception to January 2021 and supplemented by hand searches. A total of 17 studies, including two clinical trials and 15 animal studies using orthotopic pulp regeneration models, were included for the review. The risk of bias for the individual studies was assessed. This scoping review demonstrated that the regeneration of vascularized pulp-like tissue was achieved using the stem cell transplantation strategy in animal models. Autologous cell transplantation in two clinical studies also successfully regenerated vascularized vital tissue. Dental pulp stem cell subpopulations, such as mobilized dental pulp stem cells, injectable scaffolds such as atelocollagen, and a granulocyte-colony forming factor, were the most commonly used for pulp regeneration. The overall risk of bias was unclear for animal studies and was moderate or judged to raise some concerns for clinical studies. More high-quality clinical studies are needed to further determine the safety and efficacy of the stem cell transplantation strategy for dental pulp regeneration.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review

Kim

2021

IJMS

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“…DPSCs and SHED, which are derived from the pulp of teeth, possess the properties of MSCs and demonstrate the ability to differentiate into various primary cell phenotypes, such as neuronal, endothelial, and SMCs [ 5 , 35 ]. Both DPSCs and SHED have been investigated for their angiogenic potentials in tissue vascularization, vasculature engineering, and treatment of ischemic diseases [ 6 , 36 , 37 ]. However, a relatively small volume of pulp tissue available within the exfoliated deciduous compared to that within the wisdom teeth makes it much difficult to isolate sufficient cells [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

DPSCs treated by TGF-β1 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2 signaling

et al. 2021

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Background Maintaining the stability and maturation of blood vessels is of paramount importance for the vessels to carry out their physiological function. Smooth muscle cells (SMCs), pericytes, and mesenchymal stem cells (MSCs) are involved in the maturation process of the newly formed vessels. The aim of this study was to investigate whether transforming growth factor beta 1 (TGF-β1) treatment could enhance pericyte-like properties of dental pulp stem cells (DPSCs) and how TGF-β1-treated DPSCs for 7 days (T-DPSCs) stabilize the newly formed blood vessels. Methods We utilized TGF-β1 to treat DPSCs for 1, 3, 5, and 7 days. Western blotting and immunofluorescence were used to analyze the expression of SMC markers. Functional contraction assay was conducted to assess the contractility of T-DPSCs. The effects of T-DPSC-conditioned media (T-DPSC-CM) on human umbilical vein endothelial cell (HUVEC) proliferation and migration were examined by MTT, wound healing, and trans-well migration assay. Most importantly, in vitro 3D co-culture spheroidal sprouting assay was used to investigate the regulating role of vascular endothelial growth factor (VEGF)-angiopoietin (Ang)-Tie2 signaling on angiogenic sprouting in 3D co-cultured spheroids of HUVECs and T-DPSCs. Angiopoietin 2 (Ang2) and VEGF were used to treat the co-cultured spheroids to explore their roles in angiogenic sprouting. Inhibitors for Tie2 and VEGFR2 were used to block Ang1/Tie2 and VFGF/VEGFR2 signaling. Results Western blotting and immunofluorescence showed that the expression of SMC-specific markers (α-SMA and SM22α) were significantly increased after treatment with TGF-β1. Contractility of T-DPSCs was greater compared with that of DPSCs. T-DPSC-CM inhibited HUVEC migration. In vitro sprouting assay demonstrated that T-DPSCs enclosed HUVECs, resembling pericyte-like cells. Compared to co-culture with DPSCs, a smaller number of HUVEC sprouting was observed when co-cultured with T-DPSCs. VEGF and Ang2 co-stimulation significantly enhanced sprouting in HUVEC and T-DPSC co-culture spheroids, whereas VEGF or Ang2 alone exerted insignificant effects on HUVEC sprouting. Blocking Tie2 signaling reversed the sprouting inhibition by T-DPSCs, while blocking VEGF receptor (VEGFR) signaling boosted the sprouting inhibition by T-DPSCs. Conclusions This study revealed that TGF-β1 can induce DPSC differentiation into functional pericyte-like cells. T-DPSCs maintain vessel stability through Ang1/Tie2 and VEGF/VEGFR2 signaling.

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Wireless Electric Cues Mediate Autologous DPSC‐Loaded Conductive Hydrogel Microspheres to Engineer the Immuno‐Angiogenic Niche for Homologous Maxillofacial Bone Regeneration

Sun,

Xu,

et al. 2023

Adv Healthcare Materials

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Stem cell therapy serves as effective treatment for tissue regeneration. Nevertheless, stem cells from bone marrow and peripheral blood are still lacking autologous and developmental homologous properties. Dental pulp stem cells (DPSCs) from autologous deciduous tooth are derived from neural crest, in coincidence with maxillofacial tissues, thus attracting great interest in in situ maxillofacial regenerative medicine. However, insufficient number of seed cells and heterogenous alteration of cell phenotypes retard further exploration of DPSC‐based tissue engineering. Electric stimulation has recently attracted great interest in tissue regeneration. In this study, we fabricated a novel DPSC‐loaded conductive hydrogel microspheres integrated with wireless electric generator. Application of exogenous electric cues can promote stemness maintaining and heterogeneity suppression for unpredictable differentiation of encapsulated DPSCs. Further investigations observed that electric signal fine‐tunes regenerative niche by improvement on DPSC‐mediated paracrine pattern, evidenced by enhanced angiogenic behavior and upregulated anti‐inflammatory macrophage polarization. By wireless electric stimulation on implanted conductive hydrogel microspheres, loaded DPSCs facilitates the construction of immuno‐angiogenic niche at early stage of tissue repair, and further contributes to advanced autologous mandibular bone defect regeneration. Overall, a conductive microsphere is provided as stem cell carrier that facilitates the stemness maintaining and paracrine behavior of DPSCs for modulation on regenerative niche. Application of integrated charging‐conducting cell carrier on DPSC‐based tissue engineering exhibits promising translational and therapeutic potential for autologous maxillofacial tissue regeneration, and paves the way for autologous and homologous stem cell‐based tissue engineering.This article is protected by copyright. All rights reserved

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SHED promote angiogenesis in stem cell-mediated dental pulp regeneration

Cited by 37 publications

References 27 publications

A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review

A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review

DPSCs treated by TGF-β1 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2 signaling

Wireless Electric Cues Mediate Autologous DPSC‐Loaded Conductive Hydrogel Microspheres to Engineer the Immuno‐Angiogenic Niche for Homologous Maxillofacial Bone Regeneration

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