Dental Pulp Stem Cells (DPSCs) and Tissue Regeneration: Mechanisms Mediated by Direct, Paracrine or Autocrine Effects

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 13969

Special Issue Editors


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Guest Editor
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
Interests: dental pulp stem cell; mesenchymal stem cells; tissue regeneration; angiogenesis; revascularization; dental pulp organoids
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Laboratory of Experimental Medicine and Environmental Pathology, Rieti, Italy
Interests: mesenchymal stem cells; regenerative medicine; neural differentiation of stem cells; cellular prion protein
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A new source of mesenchymal stem cells, the so-called dental-pulp-derived stem cells (DPSCs), could represent an important tool for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Given their differentiation and trans-differentiation ability towards specialized cells, when properly implanted into a microenvironment they can also be involved in the regeneration and repair of tissue damaged by traumas, degenerative diseases and pathogens. The second and maybe even more important property that could expand the horizon of regenerative medicine is related to DPSCs’ immuno-modulatory functions. As matter of fact, this Special Issue aim to focus on the underlying mechanism of the regenerative potential of DPSCs that could be obtained by: (1) injured tissue substitution by differentiated DPSCs and/or (2) the de novo regeneration capability of endogenous stem cells induced by stem niche remodeling mediated by DPSCs secreted factors.

Original research articles on these and related topics are welcomed, including comprehensive reviews.

Prof. Dr. Simona Delle Monache
Dr. Vincenzo Mattei
Guest Editors

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Keywords

  • dental pulp stem cell
  • mesenchymal stem cells
  • tissue regeneration
  • angiogenesis
  • revascularization
  • dental pulp organoids

Published Papers (6 papers)

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Editorial

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4 pages, 198 KiB  
Editorial
Dental Pulp Stem Cells (DPSCs) and Tissue Regeneration: Mechanisms Mediated by Direct, Paracrine, or Autocrine Effects
by Vincenzo Mattei and Simona Delle Monache
Biomedicines 2023, 11(2), 386; https://doi.org/10.3390/biomedicines11020386 - 28 Jan 2023
Cited by 4 | Viewed by 1290
Abstract
Among mesenchymal stem cells, dental pulp stem cells (DPSCs) were discovered most recently [...] Full article

Research

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15 pages, 3145 KiB  
Article
Effects of Dentin Phosphophoryn-Derived RGD Peptides on the Differentiation and Mineralization of Human Dental Pulp Stem Cells In Vitro
by Tubayesha Hassan, Youjing Qiu, Md Riasat Hasan and Takashi Saito
Biomedicines 2022, 10(11), 2781; https://doi.org/10.3390/biomedicines10112781 - 1 Nov 2022
Cited by 1 | Viewed by 2001
Abstract
The purposes of this study were to investigate the in vitro effects of arginine-glycine-aspertic acid (RGD) peptides derived from human dentin phosphophoryn (DPP) on human dental pulp stem cell-proliferation, differentiation and mineralization, and to explore the mechanism of the peptides’ function. The 1 [...] Read more.
The purposes of this study were to investigate the in vitro effects of arginine-glycine-aspertic acid (RGD) peptides derived from human dentin phosphophoryn (DPP) on human dental pulp stem cell-proliferation, differentiation and mineralization, and to explore the mechanism of the peptides’ function. The 1 M concentration of soluble DPP-derived RGD peptides, RGD-1, RGD-2 and RGD-3 were coated onto non-tissue-culture polystyrene plates, and human dental pulp stem cells (hDPSCs) were cultured on them to examine the effects of the peptides on hDPSCs. In addition, 1 M arginine-alanine-aspertic acid (RAD) peptides were used as the control. Cell proliferation of hDPSCs was promoted by all three RGD peptides. All three RGD peptides had significantly higher alkaline phosphatase (ALP) activity compared to the control. RGD-3 induced the highest ALP activity compared to the control. RGD-3 also significantly promoted the mRNA expression of the following genes: 1.69-fold in dentine matrix protein-1 (DMP-1), 1.99-fold in dentine sialophosphoprotein (DSPP), 1.51-fold in ALP, and 2.31-fold in bone sialoprotein (BSP), as compared to the control group. Mineralization of hDPSCs was accelerated by all three RGD peptides, RGD-3 in particular. The MAPK p38 inhibitor SB202190 inhibited the effect of RGD-3 to a level comparable to the control, observed in both ALP activity assay and Arizarin red S (ARS) staining. It suggests that the p38 pathway may be responsible for eliciting the differentiation and mineralization effects of DPP-derived RGD peptides in the hDPSCs. The mRNA expression levels of the integrins ITGA1-5, ITGA7, ITGB1 and ITGB3 were significantly upregulated. Among them, expression of ITGA5 was promoted 1.9-fold, ITGA7 1.58-fold, ITGB1 1.75-fold and ITGB3 1.9-fold compared to the control. It suggests the possible involvement of these integrin channels in different subunit combinations facilitating signal transduction for differentiation of hDPSCs into odontoblasts. As conclusions, human DPP-derived RGD peptides RGD-1, RGD-2 and RGD-3 promoted the proliferation, differentiation and mineralization of hDPSCs in vitro. Among the three peptides, RGD-3 had the most significant effects. It is also suggested that RGD-3 binds to integrin receptors on the surface of hDPSCs and regulates the odontogenic gene expression and differentiation via activation of p38 of MAPK pathway. DPP-derived RGD-3 may be a promising choice in the formulation of a novel material for vital pulp therapy to induce dental pulp stem cells into odontoblasts and form reparative dentin on the exposed pulp tissue. Full article
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16 pages, 2760 KiB  
Article
Hypoxia Induces DPSC Differentiation versus a Neurogenic Phenotype by the Paracrine Mechanism
by Simona Delle Monache, Fanny Pulcini, Francesca Santilli, Stefano Martellucci, Costantino Santacroce, Jessica Fabrizi, Adriano Angelucci, Maurizio Sorice and Vincenzo Mattei
Biomedicines 2022, 10(5), 1056; https://doi.org/10.3390/biomedicines10051056 - 3 May 2022
Cited by 20 | Viewed by 2001
Abstract
As previously described by several authors, dental pulp stem cells (DPSCs), when adequately stimulated, may acquire a neuronal-like phenotype acting as a favorable source of stem cells in the generation of nerves. Besides, it is known that hypoxia conditioning is capable of stimulating [...] Read more.
As previously described by several authors, dental pulp stem cells (DPSCs), when adequately stimulated, may acquire a neuronal-like phenotype acting as a favorable source of stem cells in the generation of nerves. Besides, it is known that hypoxia conditioning is capable of stimulating cell differentiation as well as survival and self-renewal, and that multiple growth factors, including Epidermal Growth factor (EGF) and basic fibroblast growth factor (bFGF), are often involved in the induction of the neuronal differentiation of progenitor cells. In this work, we investigated the role of hypoxia in the commitment of DPSCs into a neuronal phenotype. These cells were conditioned with hypoxia (O2 1%) for 5 and 16 days; subsequently, we analyzed the proliferation rate and morphology, and tested the cells for neural and stem markers. Moreover, we verified the possible autocrine/paracrine role of DPSCs in the induction of neural differentiation by comparing the secretome profile of the hypoxic and normoxic conditioned media (CM). Our results showed that the hypoxia-mediated DPSC differentiation was time dependent. Moreover, conditioned media (CM derived from DPSCs stimulated by hypoxia were able, in turn, to induce the neural differentiation of SH-SY5Y neuroblastoma cells and undifferentiated DPSCs. In conclusion, under the herein-mentioned conditions, hypoxia seems to favor the differentiation of DPSCs into neuron-like cells. In this way, we confirm the potential clinical utility of differentiated neuronal DPSCs, and we also suggest the even greater potential of CM-derived-hypoxic DPSCs that could more readily be used in regenerative therapies. Full article
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17 pages, 3567 KiB  
Article
Investigating the Effects of Conditioned Media from Stem Cells of Human Exfoliated Deciduous Teeth on Dental Pulp Stem Cells
by Huong Thu Vu, Mi-Ran Han, Jun-Haeng Lee, Jong-Soo Kim, Ji-Sun Shin, Ji-Young Yoon, Jeong-Hui Park, Khandmaa Dashnyam, Jonathan Campbell Knowles, Hae-Hyoung Lee, Jong-Bin Kim and Jung-Hwan Lee
Biomedicines 2022, 10(4), 906; https://doi.org/10.3390/biomedicines10040906 - 15 Apr 2022
Cited by 7 | Viewed by 2997
Abstract
Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have [...] Read more.
Pulp regeneration has recently attracted interest in modern dentistry. However, the success ratio of pulp regeneration is low due to the compromising potential of stem cells, such as their survival, migration, and odontoblastic differentiation. Stem cells from human exfoliated deciduous teeth (SHED) have been considered a promising tool for regenerative therapy due to their ability to secrete multiple factors that are essential for tissue regeneration, which is achieved by minimally invasive procedures with fewer ethical or legal concerns than those of other procedures. The aim of this study is to investigate the potency of SHED-derived conditioned media (SHED CM) on dental pulp stem cells (DPSCs), a major type of mesenchymal stem cells for dental pulp regeneration. Our results show the promotive efficiency of SHED CM on the proliferation, survival rate, and migration of DPSCs in a dose-dependent manner. Upregulation of odontoblast/osteogenic-related marker genes, such as ALP, DSPP, DMP1, OCN, and RUNX2, and enhanced mineral deposition of impaired DPSCs are also observed in the presence of SHED CM. The analysis of SHED CM found that a variety of cytokines and growth factors have positive effects on cell proliferation, migration, anti-apoptosis, and odontoblast/osteogenic differentiation. These findings suggest that SHED CM could provide some benefits to DPSCs in pulp regeneration. Full article
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16 pages, 4206 KiB  
Article
Decellularized Dental Pulp, Extracellular Vesicles, and 5-Azacytidine: A New Tool for Endodontic Regeneration
by Francesca Diomede, Luigia Fonticoli, Guya Diletta Marconi, Ylenia Della Rocca, Thangavelu Soundara Rajan, Oriana Trubiani, Giovanna Murmura and Jacopo Pizzicannella
Biomedicines 2022, 10(2), 403; https://doi.org/10.3390/biomedicines10020403 - 8 Feb 2022
Cited by 16 | Viewed by 2014
Abstract
Dental pulp is a major component of the dental body that serves to maintain the tooth life and function. The aim of the present work was to develop a system that functions as a growth-permissive microenvironment for dental pulp regeneration using a decellularized [...] Read more.
Dental pulp is a major component of the dental body that serves to maintain the tooth life and function. The aim of the present work was to develop a system that functions as a growth-permissive microenvironment for dental pulp regeneration using a decellularized dental pulp (DDP) matrix, 5-Aza-2′-deoxycytidine (5-Aza), and Extracellular Vesicles (EVs) derived from human Dental Pulp Stem Cells (hDPSCs). Human dental pulps extracted from healthy teeth, scheduled to be removed for orthodontic purpose, were decellularized and then recellularized with hDPSCs. The hDPSCs were seeded on DDP and maintained under different culture conditions: basal medium (CTRL), EVs, 5-Aza, and EVs+-5-Aza. Immunofluorescence staining and Western blot analyses were performed to evaluate the proteins’ expression related to dentinogenesis, such as ALP, RUNX2, COL1A1, Vinculin, DMP1, and DSPP. Protein contents found in the DDP recellularized with hDPSCs were highly expressed in samples co-treated with EVs and 5-Aza compared to other culture conditions. This study developed a DDP matrix loaded by hDPSCs in co-treatment with EVs, which might enhance the dentinogenic differentiation with a high potentiality for endodontic regeneration. Full article
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Review

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18 pages, 1029 KiB  
Review
The Therapeutic Potential of Secreted Factors from Dental Pulp Stem Cells for Various Diseases
by Kenichi Ogata, Masafumi Moriyama, Mayu Matsumura-Kawashima, Tatsuya Kawado, Aiko Yano and Seiji Nakamura
Biomedicines 2022, 10(5), 1049; https://doi.org/10.3390/biomedicines10051049 - 2 May 2022
Cited by 10 | Viewed by 2394
Abstract
An alternative source of mesenchymal stem cells has recently been discovered: dental pulp stem cells (DPSCs), including deciduous teeth, which can thus comprise potential tools for regenerative medicine. DPSCs derive from the neural crest and are normally implicated in dentin homeostasis. The clinical [...] Read more.
An alternative source of mesenchymal stem cells has recently been discovered: dental pulp stem cells (DPSCs), including deciduous teeth, which can thus comprise potential tools for regenerative medicine. DPSCs derive from the neural crest and are normally implicated in dentin homeostasis. The clinical application of mesenchymal stem cells (MSCs) involving DPSCs contains various limitations, such as high cost, low safety, and cell handling issues, as well as invasive sample collection procedures. Although MSCs implantation offers favorable outcomes on specific diseases, implanted MSCs cannot survive for a long period. It is thus considered that their mediated mechanism of action involves paracrine effects. It has been recently reported that secreted molecules in DPSCs-conditioned media (DPSC-CM) contain various trophic factors and cytokines and that DPSC-CM are effective in models of various diseases. In the current study, we focus on the characteristics of DPSC-CM and their therapeutic potential against various disorders. Full article
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