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Cells
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Stem Cell Therapy in Oral and Maxillofacial Region
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Stem Cell Therapy in Oral and Maxillofacial Region

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Stem Cells".

Deadline for manuscript submissions: closed (29 February 2020) | Viewed by 98645

Special Issue Editor

Prof. Dr. Thimios A. Mitsiadis

E-Mail Website
Guest Editor
Institut für Orale Biologe, University of Zurich, Plattenstrasse 11, CH-8032 Zurich, Switzerland
Interests: craniofacial genetics; stem cells; teeth; imaging systems; signalling molecules; tissue regeneration; dental pathology; regenerative therapies; personalised medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Novel cell-based regenerative therapies for the reconstruction/repair of tissues and organs of the oral and maxillofacial regions such as teeth and bone are very challenging. Repair or reconstruction of teeth and maxilofacial tissues remains a significant clinical problem that requires interdisciplinary approaches in order to be solved. To date, there is not an established and reliable cell-based treatment for the repair of these tissues. Stem cells isolated from teeth or other oral tissues are able to differentiate into osteoblasts, chondrocytes, adipocytes, pericytes, and neuronal cells. The close association of stem cells with neo-vessels in orofacial diseases and their relation to molecular signaling pathways is important in their regulation in  order to form dental and maxillofacial-specific cells. The formation of new dental, bone, and epithelial tissues using regenerative therapy approaches would be a major improvement for the treatment of oral and maxillofacial diseases and traumas. These tissues are complex, since they are composed of a variety of cells that are controlled by distinct physical and molecular signals. The importance of these cues has been recognized, and the aim within the tissue engineering and biomaterials communities has been to tailor them to elicit specific biological responses.

Prof. Thimios A. Mitsiadis
Guest Editor

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Keywords

  • stem cells
  • dental pulp stem cells
  • vascularization
  • innervation
  • hard tissue formation
  • scaffolds
  • nanotechnology
  • signalling molecules
  • epithelial stem cells
  • dentin
  • bone

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Published Papers (7 papers)

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Research

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21 pages, 3311 KiB  
Article
Wnt-3a Induces Epigenetic Remodeling in Human Dental Pulp Stem Cells
by Verónica Uribe-Etxebarria, Patricia García-Gallastegui, Miguel Pérez-Garrastachu, María Casado-Andrés, Igor Irastorza, Fernando Unda, Gaskon Ibarretxe and Nerea Subirán
Cells 2020, 9(3), 652; https://doi.org/10.3390/cells9030652 - 7 Mar 2020
Cited by 28 | Viewed by 6004
Abstract
Dental pulp stem cells (DPSCs) from adult teeth show the expression of a very complete repertoire of stem pluripotency core factors and a high plasticity for cell reprogramming. Canonical Wnt and Notch signaling pathways regulate stemness and the expression of pluripotency core factors [...] Read more.
Dental pulp stem cells (DPSCs) from adult teeth show the expression of a very complete repertoire of stem pluripotency core factors and a high plasticity for cell reprogramming. Canonical Wnt and Notch signaling pathways regulate stemness and the expression of pluripotency core factors in DPSCs, and even very short-term (48 h) activations of the Wnt pathway induce a profound remodeling of DPSCs at the physiologic and metabolic levels. In this work, DPSC cultures were exposed to treatments modulating Notch and Wnt signaling, and also induced to differentiate to osteo/adipocytes. DNA methylation, histone acetylation, histone methylation, and core factor expression levels where assessed by mass spectroscopy, Western blot, and qPCR. A short-term activation of Wnt signaling by WNT-3A induced a genomic DNA demethylation, and increased histone acetylation and histone methylation in DPSCs. The efficiency of cell reprogramming methods relies on the ability to surpass the epigenetic barrier, which determines cell lineage specificity. This study brings important information about the regulation of the epigenetic barrier by Wnt signaling in DPSCs, which could contribute to the development of safer and less aggressive reprogramming methodologies with a view to cell therapy. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Oral and Maxillofacial Region)
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20 pages, 79947 KiB  
Article
Ameloblastomas Exhibit Stem Cell Potential, Possess Neurotrophic Properties, and Establish Connections with Trigeminal Neurons
by Pierfrancesco Pagella, Javier Catón, Christian T. Meisel and Thimios A. Mitsiadis
Cells 2020, 9(3), 644; https://doi.org/10.3390/cells9030644 - 6 Mar 2020
Cited by 16 | Viewed by 8072
Abstract
Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis [...] Read more.
Ameloblastomas are locally invasive and aggressive odontogenic tumors treated via surgical resection, which results in facial deformity and significant morbidity. Few studies have addressed the cellular and molecular events of ameloblastoma onset and progression, thus hampering the development of non-invasive therapeutic approaches. Tumorigenesis is driven by a plethora of factors, among which innervation has been long neglected. Recent findings have shown that innervation directly promotes tumor progression. On this basis, we investigated the molecular characteristics and neurotrophic properties of human ameloblastomas. Our results showed that ameloblastomas express dental epithelial stem cell markers, as well as components of the Notch signaling pathway, indicating persistence of stemness. We demonstrated that ameloblastomas express classical stem cell markers, exhibit stem cell potential, and form spheres. These tumors express also molecules of the Notch signaling pathway, fundamental for stem cells and their fate. Additionally, we showed that ameloblastomas express the neurotrophic factors NGF and BDNF, as well as their receptors TRKA, TRKB, and P75/NGFR, which are responsible for their innervation by trigeminal axons in vivo. In vitro studies using microfluidic devices showed that ameloblastoma cells attract and form connections with these nerves. Innervation of ameloblastomas might play a key role in the onset of this malignancy and might represent a promising target for non-invasive pharmacological interventions. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Oral and Maxillofacial Region)
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21 pages, 4095 KiB  
Article
Angiogenic Effects of Human Dental Pulp and Bone Marrow-Derived Mesenchymal Stromal Cells and their Extracellular Vesicles
by Greet Merckx, Baharak Hosseinkhani, Sören Kuypers, Sarah Deville, Joy Irobi, Inge Nelissen, Luc Michiels, Ivo Lambrichts and Annelies Bronckaers
Cells 2020, 9(2), 312; https://doi.org/10.3390/cells9020312 - 28 Jan 2020
Cited by 58 | Viewed by 7085
Abstract
Blood vessel formation or angiogenesis is a key process for successful tooth regeneration. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) possess paracrine proangiogenic properties, which are, at least partially, induced by their extracellular vesicles (EVs). However, the isolation of BM-MSCs is associated with several [...] Read more.
Blood vessel formation or angiogenesis is a key process for successful tooth regeneration. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) possess paracrine proangiogenic properties, which are, at least partially, induced by their extracellular vesicles (EVs). However, the isolation of BM-MSCs is associated with several drawbacks, which could be overcome by MSC-like cells of the teeth, called dental pulp stromal cells (DPSCs). This study aims to compare the angiogenic content and functions of DPSC and BM-MSC EVs and conditioned medium (CM). The angiogenic protein profile of DPSC- and BM-MSC-derived EVs, CM and EV-depleted CM was screened by an antibody array and confirmed by ELISA. Functional angiogenic effects were tested in transwell migration and chicken chorioallantoic membrane assays. All secretion fractions contained several pro- and anti-angiogenic proteins and induced in vitro endothelial cell motility. This chemotactic potential was higher for (EV-depleted) CM, compared to EVs with a stronger effect for BM-MSCs. Finally, BM-MSC CM, but not DPSC CM, nor EVs, increased in ovo angiogenesis. In conclusion, we showed that DPSCs are less potent in relation to endothelial cell chemotaxis and in ovo neovascularization, compared to BM-MSCs, which emphasizes the importance of choice of cell type and secretion fraction for stem cell-based regenerative therapies in inducing angiogenesis. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Oral and Maxillofacial Region)
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14 pages, 3059 KiB  
Article
Dental Epithelial Stem Cells as a Source for Mammary Gland Regeneration and Milk Producing Cells In Vivo
by Lucia Jimenez-Rojo, Pierfrancesco Pagella, Hidemitsu Harada and Thimios A. Mitsiadis
Cells 2019, 8(10), 1302; https://doi.org/10.3390/cells8101302 - 22 Oct 2019
Cited by 9 | Viewed by 31857
Abstract
The continuous growth of rodent incisors is ensured by clusters of mesenchymal and epithelial stem cells that are located at the posterior part of these teeth. Genetic lineage tracing studies have shown that dental epithelial stem cells (DESCs) are able to generate all [...] Read more.
The continuous growth of rodent incisors is ensured by clusters of mesenchymal and epithelial stem cells that are located at the posterior part of these teeth. Genetic lineage tracing studies have shown that dental epithelial stem cells (DESCs) are able to generate all epithelial cell populations within incisors during homeostasis. However, it remains unclear whether these cells have the ability to adopt alternative fates in response to extrinsic factors. Here, we have studied the plasticity of DESCs in the context of mammary gland regeneration. Transplantation of DESCs together with mammary epithelial cells into the mammary stroma resulted in the formation of chimeric ductal epithelial structures in which DESCs adopted all the possible mammary fates including milk-producing alveolar cells. In addition, when transplanted without mammary epithelial cells, DESCs developed branching rudiments and cysts. These in vivo findings demonstrate that when outside their niche, DESCs redirect their fates according to their new microenvironment and thus can contribute to the regeneration of non-dental tissues. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Oral and Maxillofacial Region)
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13 pages, 11034 KiB  
Article
Physiological Expression of Ion Channel Receptors in Human Periodontal Ligament Stem Cells
by Luigi Chiricosta, Francesca Diomede, Oriana Trubiani, Placido Bramanti and Emanuela Mazzon
Cells 2019, 8(3), 219; https://doi.org/10.3390/cells8030219 - 6 Mar 2019
Cited by 4 | Viewed by 3779
Abstract
The etiopathogenesis of neurodegenerative diseases is characterized by the death of neurons. Human periodontal ligament stem cells (hPDLSCs), coming from neuronal crest, can potentially become neuronal cells because of their embryologic origin. In this study, we performed an RNA-seq analysis of hPDLSCs in [...] Read more.
The etiopathogenesis of neurodegenerative diseases is characterized by the death of neurons. Human periodontal ligament stem cells (hPDLSCs), coming from neuronal crest, can potentially become neuronal cells because of their embryologic origin. In this study, we performed an RNA-seq analysis of hPDLSCs in order to determine whether their transcriptomic profile revealed genes encoded for ion channel receptors. Next, each found gene was enriched by the information of pathways stored in the Reactome database. Our results show that the hPDLSCs express GABBR1 and GABBR2, CHRNA1, GRINA genes, respectively associated with GABAB, NMDA and nACh receptors. In particular, the two subunits of GABAB receptor are expressed in hPDLSCs. Further, the proteic extract for GABABR1, GABABR2 and AChRα1 confirmed their expression in hPDLSCs. Our results show that hPDLSCs express physiologically genes associated with ion channel receptors maintaining multipotent features which are useful for neurogenesis. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Oral and Maxillofacial Region)
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Review

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19 pages, 1741 KiB  
Review
Physiology, Pathology and Regeneration of Salivary Glands
by Cristina Porcheri and Thimios A. Mitsiadis
Cells 2019, 8(9), 976; https://doi.org/10.3390/cells8090976 - 26 Aug 2019
Cited by 114 | Viewed by 22124
Abstract
Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune diseases, infections and physical traumas, can alter the functionality of these glands, greatly impacting the quality of life of patients. To date, no definitive therapeutic approach [...] Read more.
Salivary glands are essential structures in the oral cavity. A variety of diseases, such as cancer, autoimmune diseases, infections and physical traumas, can alter the functionality of these glands, greatly impacting the quality of life of patients. To date, no definitive therapeutic approach can compensate the impairment of salivary glands, and treatment are purely symptomatic. Understanding the cellular and molecular control of salivary glands function is, therefore, highly relevant for therapeutic purposes. In this review, we provide a starting platform for future studies in basic biology and clinical research, reporting classical ideas on salivary gland physiology and recently developed technology to guide regeneration, reconstruction and substitution of the functional organs. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Oral and Maxillofacial Region)
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24 pages, 8777 KiB  
Review
Periodontal Bone-Ligament-Cementum Regeneration via Scaffolds and Stem Cells
by Jin Liu, Jianping Ruan, Michael D. Weir, Ke Ren, Abraham Schneider, Ping Wang, Thomas W. Oates, Xiaofeng Chang and Hockin H. K. Xu
Cells 2019, 8(6), 537; https://doi.org/10.3390/cells8060537 - 4 Jun 2019
Cited by 183 | Viewed by 18316
Abstract
Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal [...] Read more.
Periodontitis is a prevalent infectious disease worldwide, causing the damage of periodontal support tissues, which can eventually lead to tooth loss. The goal of periodontal treatment is to control the infections and reconstruct the structure and function of periodontal tissues including cementum, periodontal ligament (PDL) fibers, and bone. The regeneration of these three types of tissues, including the re-formation of the oriented PDL fibers to be attached firmly to the new cementum and alveolar bone, remains a major challenge. This article represents the first systematic review on the cutting-edge researches on the regeneration of all three types of periodontal tissues and the simultaneous regeneration of the entire bone-PDL-cementum complex, via stem cells, bio-printing, gene therapy, and layered bio-mimetic technologies. This article primarily includes bone regeneration; PDL regeneration; cementum regeneration; endogenous cell-homing and host-mobilized stem cells; 3D bio-printing and generation of the oriented PDL fibers; gene therapy-based approaches for periodontal regeneration; regenerating the bone-PDL-cementum complex via layered materials and cells. These novel developments in stem cell technology and bioactive and bio-mimetic scaffolds are highly promising to substantially enhance the periodontal regeneration including both hard and soft tissues, with applicability to other therapies in the oral and maxillofacial region. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Oral and Maxillofacial Region)
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