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Biomolecules
Special Issues
Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells
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Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological and Bio- Materials".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 14292

Special Issue Editors

Prof. Dr. Taneaki Nakagawa

E-Mail Website
Guest Editor
Department of Dentistry and Oral Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
Interests: tissue engineering; biomaterials; oral diseases
Special Issues, Collections and Topics in MDPI journals
Dr. Takehito Ouchi

E-Mail Website
Guest Editor
Department of Physiology, Tokyo Dental College, 2-9-18, Kanda-Misaki-cho, Chiyoda-ku, Tokyo 101-0061, Japan
Interests: cancer stem cells; homeostasis; genetic regulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advanced technology in oral biology provides several options for therapeutic strategies. Application of stem cells is a powerful tool, and oral and dental mesenchymal stem cells have been studied in order to be utilized for cell therapies for decades. However, there is still a huge gap between ideal use and reality. The only way to activate and further establish this field is to continue studying stem cells combined with biomaterials and the concept of tissue engineering. Further, industry–academia collaboration will strengthen research productivity. 

In this Special Issue, we expect exciting research and review articles to promote therapeutic strategy using oral mesenchymal stem cells.

Prof. Dr. Taneaki Nakagawa
Dr. Takehito Ouchi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • mesenchymal stem cells
  • tissue engineering
  • regenerative therapy

Related Special Issue

Published Papers (7 papers)

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Editorial

Jump to: Research, Review

5 pages, 209 KiB  
Editorial
Cellular Signaling for Dental Physiological Functions
by Takehito Ouchi and Taneaki Nakagawa
Biomolecules 2023, 13(8), 1177; https://doi.org/10.3390/biom13081177 - 28 Jul 2023
Viewed by 1041
Abstract
Teeth are unique and multifaceted tissues that are necessary for routine functions, such as crushing food and constructing articulated sounds, as well as for esthetic symbols [...] Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells)

Research

Jump to: Editorial, Review

17 pages, 9964 KiB  
Article
Functional Expression of IP, 5-HT4, D1, A2A, and VIP Receptors in Human Odontoblast Cell Line
by Eri Kitayama, Maki Kimura, Takehito Ouchi, Masahiro Furusawa and Yoshiyuki Shibukawa
Biomolecules 2023, 13(6), 879; https://doi.org/10.3390/biom13060879 - 23 May 2023
Cited by 1 | Viewed by 1475
Abstract
Odontoblasts are involved in sensory generation as sensory receptor cells and in dentin formation. We previously reported that an increase in intracellular cAMP levels by cannabinoid 1 receptor activation induces Ca2+ influx via transient receptor potential vanilloid subfamily member 1 channels in [...] Read more.
Odontoblasts are involved in sensory generation as sensory receptor cells and in dentin formation. We previously reported that an increase in intracellular cAMP levels by cannabinoid 1 receptor activation induces Ca2+ influx via transient receptor potential vanilloid subfamily member 1 channels in odontoblasts, indicating that intracellular cAMP/Ca2+ signal coupling is involved in dentinal pain generation and reactionary dentin formation. Here, intracellular cAMP dynamics in cultured human odontoblasts were investigated to understand the detailed expression patterns of the intracellular cAMP signaling pathway activated by the Gs protein-coupled receptor and to clarify its role in cellular functions. The presence of plasma membrane Gαs as well as prostaglandin I2 (IP), 5-hydroxytryptamine 5-HT4 (5-HT4), dopamine D1 (D1), adenosine A2A (A2A), and vasoactive intestinal polypeptide (VIP) receptor immunoreactivity was observed in human odontoblasts. In the presence of extracellular Ca2+, the application of agonists for the IP (beraprost), 5-HT4 (BIMU8), D1 (SKF83959), A2A (PSB0777), and VIP (VIP) receptors increased intracellular cAMP levels. This increase in cAMP levels was inhibited by the application of the adenylyl cyclase (AC) inhibitor SQ22536 and each receptor antagonist, dose-dependently. These results suggested that odontoblasts express Gs protein-coupled IP, 5-HT4, D1, A2A, and VIP receptors. In addition, activation of these receptors increased intracellular cAMP levels by activating AC in odontoblasts. Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells)
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16 pages, 3068 KiB  
Article
Insights into the Structure and Function of TRIP-1, a Newly Identified Member in Calcified Tissues
by Jaison Arivalagan, Amudha Ganapathy, Kalimuthu Kalishwaralal, Yinghua Chen and Anne George
Biomolecules 2023, 13(3), 412; https://doi.org/10.3390/biom13030412 - 22 Feb 2023
Cited by 1 | Viewed by 1650
Abstract
Eukaryotic initiation factor subunit I (EIF3i), also called as p36 or TRIP-1, is a component of the translation initiation complex and acts as a modulator of TGF-β signaling. We demonstrated earlier that this intracellular protein is not only exported to the extracellular matrix [...] Read more.
Eukaryotic initiation factor subunit I (EIF3i), also called as p36 or TRIP-1, is a component of the translation initiation complex and acts as a modulator of TGF-β signaling. We demonstrated earlier that this intracellular protein is not only exported to the extracellular matrix via exosomes but also binds calcium phosphate and promotes hydroxyapatite nucleation. To assess other functional roles of TRIP-1, we first examined their phylogeny and showed that it is highly conserved in eukaryotes. Comparing human EIF3i sequence with that of 63 other eukaryotic species showed that more than 50% of its sequence is conserved, suggesting the preservation of its important functional role (translation initiation) during evolution. TRIP-1 contains WD40 domains and predicting its function based on this structural motif is difficult as it is present in a vast array of proteins with a wide variety of functions. Therefore, bioinformatics analysis was performed to identify putative regulatory functions for TRIP-1 by examining the structural domains and post-translational modifications and establishing an interactive network using known interacting partners such as type I collagen. Insight into the function of TRIP-1 was also determined by examining structurally similar proteins such as Wdr5 and GPSß, which contain a ß-propeller structure which has been implicated in the calcification process. Further, proteomic analysis of matrix vesicles isolated from TRIP-1-overexpressing preosteoblastic MC3T3-E1 cells demonstrated the expression of several key biomineralization-related proteins, thereby confirming its role in the calcification process. Finally, we demonstrated that the proteomic signature in TRIP1-OE MVs facilitated osteogenic differentiation of stem cells. Overall, we demonstrated by bioinformatics that TRIP-1 has a unique structure and proteomic analysis suggested that the unique osteogenic cargo within the matrix vesicles facilitates matrix mineralization. Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells)
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14 pages, 2680 KiB  
Article
Gαs-Coupled CGRP Receptor Signaling Axis from the Trigeminal Ganglion Neuron to Odontoblast Negatively Regulates Dentin Mineralization
by Natsuki Saito, Maki Kimura, Takehito Ouchi, Tatsuya Ichinohe and Yoshiyuki Shibukawa
Biomolecules 2022, 12(12), 1747; https://doi.org/10.3390/biom12121747 - 24 Nov 2022
Cited by 5 | Viewed by 1821
Abstract
An inflammatory response following dental pulp injury and/or infection often leads to neurogenic inflammation via the axon reflex. However, the detailed mechanism underlying the occurrence of the axon reflex in the dental pulp remains unclear. We sought to examine the intracellular cyclic adenosine [...] Read more.
An inflammatory response following dental pulp injury and/or infection often leads to neurogenic inflammation via the axon reflex. However, the detailed mechanism underlying the occurrence of the axon reflex in the dental pulp remains unclear. We sought to examine the intracellular cyclic adenosine monophosphate (cAMP) signaling pathway in odontoblasts via the activation of Gs protein-coupled receptors and intercellular trigeminal ganglion (TG) neuron–odontoblast communication following direct mechanical stimulation of TG neurons. Odontoblasts express heterotrimeric G-protein α-subunit Gαs and calcitonin receptor-like receptors. The application of an adenylyl cyclase (AC) activator and a calcitonin gene-related peptide (CGRP) receptor agonist increased the intracellular cAMP levels ([cAMP]i) in odontoblasts, which were significantly inhibited by the selective CGRP receptor antagonist and AC inhibitor. Mechanical stimulation of the small-sized CGRP-positive but neurofilament heavy chain-negative TG neurons increased [cAMP]i in odontoblasts localized near the stimulated neuron. This increase was inhibited by the CGRP receptor antagonist. In the mineralization assay, CGRP impaired the mineralization ability of the odontoblasts, which was reversed by treatment with a CGRP receptor antagonist and AC inhibitor. CGRP establishes an axon reflex in the dental pulp via intercellular communication between TG neurons and odontoblasts. Overall, CGRP and cAMP signaling negatively regulate dentinogenesis as defensive mechanisms. Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells)
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Review

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16 pages, 325 KiB  
Review
Growth Factor Delivery Using a Collagen Membrane for Bone Tissue Regeneration
by Tadahiro Takayama, Kentaro Imamura and Seiichi Yamano
Biomolecules 2023, 13(5), 809; https://doi.org/10.3390/biom13050809 - 10 May 2023
Cited by 2 | Viewed by 1927
Abstract
The use of biomaterials and bioactive agents has shown promise in bone defect repair, leading to the development of strategies for bone regeneration. Various artificial membranes, especially collagen membranes (CMs) that are widely used for periodontal therapy and provide an extracellular matrix-simulating environment, [...] Read more.
The use of biomaterials and bioactive agents has shown promise in bone defect repair, leading to the development of strategies for bone regeneration. Various artificial membranes, especially collagen membranes (CMs) that are widely used for periodontal therapy and provide an extracellular matrix-simulating environment, play a significant role in promoting bone regeneration. In addition, numerous growth factors (GFs) have been used as clinical applications in regenerative therapy. However, it has been established that the unregulated administration of these factors may not work to their full regenerative potential and could also trigger unfavorable side effects. The utilization of these factors in clinical settings is still restricted due to the lack of effective delivery systems and biomaterial carriers. Hence, considering the efficiency of bone regeneration, both spaces maintained using CMs and GFs can synergistically create successful outcomes in bone tissue engineering. Therefore, recent studies have demonstrated a significant interest in the potential of combining CMs and GFs to effectively promote bone repair. This approach holds great promise and has become a focal point in our research. The purpose of this review is to highlight the role of CMs containing GFs in the regeneration of bone tissue, and to discuss their use in preclinical animal models of regeneration. Additionally, the review addresses potential concerns and suggests future research directions for growth factor therapy in the field of regenerative science. Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells)
18 pages, 1389 KiB  
Review
Protective Actions in Apical Periodontitis: The Regenerative Bioactivities Led by Mesenchymal Stem Cells
by Ping Lyu, Yiming Song, Ruiye Bi, Zucen Li, Yali Wei, Qin Huang, Chen Cui, Dongzhe Song, Xuedong Zhou and Yi Fan
Biomolecules 2022, 12(12), 1737; https://doi.org/10.3390/biom12121737 - 23 Nov 2022
Cited by 6 | Viewed by 2744
Abstract
Resulting from bacterial infection, apical periodontitis (AP) is a common inflammatory disease of the periapical region of the tooth. The regeneration of the destroyed periapical alveolar bone and the surrounding periodontium tissues has long been a difficult task in clinical practice. These lesions [...] Read more.
Resulting from bacterial infection, apical periodontitis (AP) is a common inflammatory disease of the periapical region of the tooth. The regeneration of the destroyed periapical alveolar bone and the surrounding periodontium tissues has long been a difficult task in clinical practice. These lesions are closely related to pathogen invasion and an overreactive immune response. It is worth noting that the protective healing process occurs simultaneously, in which mesenchymal stem cells (MSCs) have a crucial function in mediating the immune system and promoting regeneration. Here, we review the recent studies related to AP, with a focus on the regulatory network of MSCs. We also discuss the potential therapeutic approaches of MSCs in inflammatory diseases to provide a basis for promoting tissue regeneration and modulating inflammation in AP. A deeper understanding of the protective action of MSCs and the regulatory networks will help to delineate the underlying mechanisms of AP and pave the way for stem-cell-based regenerative medicine in the future. Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells)
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16 pages, 1581 KiB  
Review
Primary Cilia: The New Face of Craniofacial Research
by Emily R. Moore
Biomolecules 2022, 12(12), 1724; https://doi.org/10.3390/biom12121724 - 22 Nov 2022
Cited by 6 | Viewed by 2745
Abstract
The primary cilium is a solitary, sensory organelle that extends from the surface of nearly every vertebrate cell, including craniofacial cells. This organelle converts chemical and physical external stimuli into intracellular signaling cascades and mediates several well-known signaling pathways simultaneously. Thus, the primary [...] Read more.
The primary cilium is a solitary, sensory organelle that extends from the surface of nearly every vertebrate cell, including craniofacial cells. This organelle converts chemical and physical external stimuli into intracellular signaling cascades and mediates several well-known signaling pathways simultaneously. Thus, the primary cilium is considered a cellular signaling nexus and amplifier. Primary cilia dysfunction directly results in a collection of diseases and syndromes that typically affect multiple organ systems, including the face and teeth. Despite this direct connection, primary cilia are largely unexplored in craniofacial research. In this review, I briefly summarize craniofacial abnormalities tied to the primary cilium and examine the existing information on primary cilia in craniofacial development and repair. I close with a discussion on preliminary studies that motivate future areas of exploration that are further supported by studies performed in long bone and kidney cells. Full article
(This article belongs to the Special Issue Advanced Therapeutic Strategies via Oral Mesenchymal Stem Cells)
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