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Special Issue "Stem Cells from Dental Sources: Translational Applications in Medicine and Novel Approaches"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 April 2021).

Special Issue Editors

Prof. Dr. Antonio Frigeri
E-Mail Website
Guest Editor
1. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy
2. Dominck Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA
Interests: brain water homeostasis; evaluation of the different aquaporin-4 isoforms in the expression; polarization and water channel activity at the BBB level and in brain tumors
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Antonio Rampino
E-Mail Website
Guest Editor
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy
Interests: Neuroscience; translational psychiatry; stem cells; rigenerative medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Fabio Sallustio
E-Mail Website
Guest Editor
Department of Interdisciplinary Medicine, University of Bari, Bari, Italy
Interests: Regenerative medicine; mesenchymal stem cells; amniotic stem cells tissue engineering; stem cell reparative mechanisms
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tissue engineering was initially based on the use of mesenchymal stem cells (MSCs) from specific sites, such as the spinal cord or umbilical cord, and biomaterials, even more biomimetic and bioactive. The searching for new biological sites, easily accessible, and rich in stem cells, has led to the discovery of numerous novel types of stem cells, alternatives to those considered as "gold standard". Recently, oral tissues have been investigated as a smart source of stem cells. MSCs isolated from human periapical cysts, for example, have been recently isolated and termed “human Periapical Cyst-MSCs” (hPCy-MSCs): they represent an innovative source of stem cells obtained from a "biological waste", able to differentiate towards both osteogenic and neurogenic lineages. Future challenges will be focused on the development of regenerative strategies with dental-derived stem cells, aimed at the overcoming the current biological limitations, to promote performing and predictable clinical results.

Contributions on these and related topics are welcomed, including original research articles and full and mini-reviews. We also very much welcome papers from postdocs, PhD students, and young researchers.

Prof. Dr. Marco Tatullo 
Prof. Dr. Antonio Frigeri
Prof. Dr. Antonio Rampino
Prof. Dr. Fabio Sallustio
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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • Regenerative medicine
  • Regenerative dentistry
  • Biomimetic materials
  • Dental stem cells
  • Tissue engineering

Published Papers (7 papers)

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Research

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Article
Effect of Inducible BMP-7 Expression on the Osteogenic Differentiation of Human Dental Pulp Stem Cells
Int. J. Mol. Sci. 2021, 22(12), 6182; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126182 - 08 Jun 2021
Viewed by 818
Abstract
BMP-7 has shown inductive potential for in vitro osteogenic differentiation of mesenchymal stem cells, which are an ideal resource for regenerative medicine. Externally applied, recombinant BMP-7 was able to induce the osteogenic differentiation of DPSCs but based on our previous results with BMP-2, [...] Read more.
BMP-7 has shown inductive potential for in vitro osteogenic differentiation of mesenchymal stem cells, which are an ideal resource for regenerative medicine. Externally applied, recombinant BMP-7 was able to induce the osteogenic differentiation of DPSCs but based on our previous results with BMP-2, we aimed to study the effect of the tetracyclin-inducible BMP-7 expression on these cells. DPSC, mock, and DPSC-BMP-7 cell lines were cultured in the presence or absence of doxycycline, then alkaline phosphatase (ALP) activity, mineralization, and mRNA levels of different osteogenic marker genes were measured. In the DPSC-BMP-7 cell line, the level of BMP-7 mRNA significantly increased in the media supplemented with doxycycline, however, the expression of Runx2 and noggin genes was upregulated only after 21 days of incubation in the osteogenic medium with doxycycline. Moreover, while the examination of ALP activity showed reduced activity in the control medium containing doxycycline, the accumulation of minerals remained unchanged in the cultures. We have found that the induced BMP-7 expression failed to induce osteogenic differentiation of DPSCs. We propose three different mechanisms that may worth investigating for the engineering of expression systems that can be used for the induction of differentiation of mesenchymal stem cells. Full article
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Article
The Effects of Cryogenic Storage on Human Dental Pulp Stem Cells
Int. J. Mol. Sci. 2021, 22(9), 4432; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094432 - 23 Apr 2021
Cited by 1 | Viewed by 617
Abstract
Dental pulp stem cells (DPSCs) are a type of easily accessible adult mesenchymal stem cell. Due to their ease of access, DPSCs show great promise in regenerative medicine. However, the tooth extractions from which DPSCs can be obtained are usually performed at a [...] Read more.
Dental pulp stem cells (DPSCs) are a type of easily accessible adult mesenchymal stem cell. Due to their ease of access, DPSCs show great promise in regenerative medicine. However, the tooth extractions from which DPSCs can be obtained are usually performed at a period of life when donors would have no therapeutic need of them. For this reason, it is imperative that successful stem cell storage techniques are employed so that these cells remain viable for future use. Any such techniques must result in high post-thaw stem cell recovery without compromising stemness, proliferation, or multipotency. Uncontrolled-rate freezing is not a technically or financially demanding technique compared to expensive and laborious controlled-rate freezing techniques. This study was aimed at observing the effect of uncontrolled-rate freezing on DPSCs stored for 6 and 12 months. Dimethyl sulfoxide at a concentration of 10% was used as a cryoprotective agent. Various features such as shape, proliferation capacity, phenotype, and multipotency were studied after DPSC thawing. The DPSCs did not compromise their stemness, viability, proliferation, or differentiating capabilities, even after one year of cryopreservation at −80 °C. After thawing, they retained their stemness markers and low-level expression of hematopoietic markers. We observed a size reduction in recovery DPSCs after one year of storage. This observation indicates that DPSCs can be successfully used in potential clinical applications, even after a year of uncontrolled cryopreservation. Full article
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Article
Interleukin-1β Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces
Int. J. Mol. Sci. 2021, 22(3), 1027; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031027 - 20 Jan 2021
Cited by 7 | Viewed by 1033
Abstract
The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of [...] Read more.
The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of MMPs and TIMPs is influenced by the aseptic inflammation occurring during orthodontic treatment. Interleukin (IL)-1β is one of the most abundant inflammatory mediators in this process and crucially affects the expression of MMPs and TIMPs in the presence of cyclic low-magnitude orthodontic tensile forces. In this study we aimed to investigate, for the first time, how IL-1β induced expression of MMPs, TIMPs and how IL-1β in hPDL-MSCs was changed after applying in vitro low-magnitude orthodontic tensile strains in a static application mode. Hence, primary hPDL-MSCs were stimulated with IL-1β in combination with static tensile strains (STS) with 6% elongation. After 6- and 24 h, MMP-1, MMP-2, TIMP-1 and IL-1β expression levels were measured. STS alone had no influence on the basal expression of investigated target genes, whereas IL-1β caused increased expression of these genes. In combination, they increased the gene and protein expression of MMP-1 and the gene expression of MMP-2 after 24 h. After 6 h, STS reduced IL-1β-induced MMP-1 synthesis and MMP-2 gene expression. IL-1β-induced TIMP-1 gene expression was decreased by STS after 6- and 24-h. At both time points, the IL-1β-induced gene expression of IL-1β was increased. Additionally, this study showed that fetal bovine serum (FBS) caused an overall suppression of IL-1β-induced expression of MMP-1, MMP-2 and TIMP-1. Further, it caused lower or opposite effects of STS on IL-1β-induced expression. These observations suggest that low-magnitude orthodontic tensile strains may favor a more inflammatory and destructive response of hPDL-MSCs when using a static application form and that this response is highly influenced by the presence of FBS in vitro. Full article
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Article
rhBMP-2 Pre-Treated Human Periodontal Ligament Stem Cell Sheets Regenerate a Mineralized Layer Mimicking Dental Cementum
Int. J. Mol. Sci. 2020, 21(11), 3767; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21113767 - 26 May 2020
Cited by 9 | Viewed by 1401
Abstract
The periodontal complex consisting of alveolar bone, cementum, and periodontal ligaments (PDL) supports human teeth through the systematic orchestration of mineralized tissues and fibrous tissues. Importantly, cementum, the outermost mineralized layer of dental roots, plays an essential role by bridging the inner ligaments [...] Read more.
The periodontal complex consisting of alveolar bone, cementum, and periodontal ligaments (PDL) supports human teeth through the systematic orchestration of mineralized tissues and fibrous tissues. Importantly, cementum, the outermost mineralized layer of dental roots, plays an essential role by bridging the inner ligaments from the dental root to the alveolar bone. When the periodontal complex is damaged, the regeneration of each component of the periodontal complex is necessary; however, it is still challenging to achieve complete functional regeneration. In this study, we tried to control the regeneration of cementum and PDL by using a human PDL stem cell (hPDLSC) sheet engineering technology with the pretreatment of recombinant human BMP-2 (rhBMP-2). Isolated hPDLSCs obtained from extracted human teeth were pretreated with rhBMP-2 for in vitro osteogenic differentiation and grafted on the micro/macro-porous biphasic calcium phosphate (MBCP) blocks, which represent dental roots. The MBCPs with hPDLSC sheets were implanted in the subcutaneous layer of immune-compromised mice, and rhBMP-2 pretreated hPDLSC sheets showed higher mineralization and collagen ligament deposition than the no-pretreatment group. Therefore, the rhBMP-2-hPDLSC sheet technique could be an effective strategy for the synchronized regeneration of two different tissues: mineralized tissue and fibrous tissues in periodontal complexes. Full article
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Review

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Review
Sinking Our Teeth in Getting Dental Stem Cells to Clinics for Bone Regeneration
Int. J. Mol. Sci. 2021, 22(12), 6387; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126387 - 15 Jun 2021
Cited by 1 | Viewed by 990
Abstract
Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for [...] Read more.
Dental stem cells have been isolated from the medical waste of various dental tissues. They have been characterized by numerous markers, which are evaluated herein and differentiated into multiple cell types. They can also be used to generate cell lines and iPSCs for long-term in vitro research. Methods for utilizing these stem cells including cellular systems such as organoids or cell sheets, cell-free systems such as exosomes, and scaffold-based approaches with and without drug release concepts are reported in this review and presented with new pictures for clarification. These in vitro applications can be deployed in disease modeling and subsequent pharmaceutical research and also pave the way for tissue regeneration. The main focus herein is on the potential of dental stem cells for hard tissue regeneration, especially bone, by evaluating their potential for osteogenesis and angiogenesis, and the regulation of these two processes by growth factors and environmental stimulators. Current in vitro and in vivo publications show numerous benefits of using dental stem cells for research purposes and hard tissue regeneration. However, only a few clinical trials currently exist. The goal of this review is to pinpoint this imbalance and encourage scientists to pick up this research and proceed one step further to translation. Full article
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Review
A Cell-Based Approach to Dental Pulp Regeneration Using Mesenchymal Stem Cells: A Scoping Review
Int. J. Mol. Sci. 2021, 22(9), 4357; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094357 - 22 Apr 2021
Cited by 1 | Viewed by 907
Abstract
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 [...] Read more.
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. Full article
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Review
Dental Pulp-Derived Mesenchymal Stem Cells for Modeling Genetic Disorders
Int. J. Mol. Sci. 2021, 22(5), 2269; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052269 - 25 Feb 2021
Viewed by 925
Abstract
A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, [...] Read more.
A subpopulation of mesenchymal stem cells, developmentally derived from multipotent neural crest cells that form multiple facial tissues, resides within the dental pulp of human teeth. These stem cells show high proliferative capacity in vitro and are multipotent, including adipogenic, myogenic, osteogenic, chondrogenic, and neurogenic potential. Teeth containing viable cells are harvested via minimally invasive procedures, based on various clinical diagnoses, but then usually discarded as medical waste, indicating the relatively low ethical considerations to reuse these cells for medical applications. Previous studies have demonstrated that stem cells derived from healthy subjects are an excellent source for cell-based medicine, tissue regeneration, and bioengineering. Furthermore, stem cells donated by patients affected by genetic disorders can serve as in vitro models of disease-specific genetic variants, indicating additional applications of these stem cells with high plasticity. This review discusses the benefits, limitations, and perspectives of patient-derived dental pulp stem cells as alternatives that may complement other excellent, yet incomplete stem cell models, such as induced pluripotent stem cells, together with our recent data. Full article
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