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Cells
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Oral Tissue Stem Cells in Regenerative Dentistry
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Oral Tissue Stem Cells in Regenerative Dentistry

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

Deadline for manuscript submissions: 15 May 2025 | Viewed by 8528

Special Issue Editors

Prof. Dr. Jelena Milasin

E-Mail Website
Guest Editor
Department of Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Dr. Subotica 8, 11000 Belgrade, Serbia
Interests: medical genetics; cancer molecular biology; cancer genetics; stem cell research
Special Issues, Collections and Topics in MDPI journals
Dr. Miloš M. Lazarević

E-Mail Website
Guest Editor
Department of Human Genetics, School of Dental Medicine, University of Belgrade, Belgrade, Dr. Subotica 8, 11000 Belgrade, Serbia
Interests: dental stem cells; molecular biology; dental biomaterials

Special Issue Information

Dear Colleagues,

Regenerative dentistry has forced modern dentistry to improve its clinical and scientific efforts during the past ten years. Adult stem cells known as mesenchymal stem cells have strong immunoregulatory and regeneration abilities. Among the accessible sources of MSC are dental tissues. Dental pulp, apical papilla, dental follicle, and periodontal ligament-derived dental stem cells (DSCs), to name a few, represent very promising cell supplies for the regeneration of a variety of tissues and organs. Meanwhile, newly developed dental materials in conjunction with DSC-derived bioactive compounds (e.g., extracellular vesicles) have been used for orofacial tissue repair in experimental research and clinical practice.

Successful tissue engineering strategies require a profound understanding of the DSCs’ biology and their behavior in the presence of various biomaterials for wider clinical applications. The scientific knowledge gained from this Special Issue will serve as an important foundation for upcoming research and the development of DSCs-based therapeutic tools in regenerative dentistry.

This Special Issue aims to collect manuscripts that offer insights on topics related to the use of oral tissue stem cells, regenerative medicine, orofacial tissue repair, and dental materials for tissue regeneration. The manuscripts can be original research articles, reviews, or other types of writing.

Various types of research, including experimental and preclinical investigations, are welcomed.

We look forward to your contributions.

Prof. Dr. Jelena Milasin
Dr. Miloš M. Lazarević
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. Cells is an international peer-reviewed open access semimonthly 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

  • oral tissue stem cells
  • oral tissue regeneration
  • dental materials
  • stem cell-derived exosomes
  • stem cell engineering

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Published Papers (5 papers)

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Research

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15 pages, 1971 KiB  
Article
RNAseq of Gingival Fibroblasts Exposed to PRF Membrane Lysates and PRF Serum
by Atefe Imani, Layla Panahipour, Hannes Kühtreiber, Michael Mildner and Reinhard Gruber
Cells 2024, 13(15), 1308; https://doi.org/10.3390/cells13151308 - 5 Aug 2024
Viewed by 1134
Abstract
Platelet-rich fibrin (PRF) is prepared by spontaneous coagulation of fractionated blood. When squeezed between two plates, PRF is separated into solid PRF membranes and a liquid exudate, the PRF serum. The question arises regarding how much the overall activity remains in the PRF [...] Read more.
Platelet-rich fibrin (PRF) is prepared by spontaneous coagulation of fractionated blood. When squeezed between two plates, PRF is separated into solid PRF membranes and a liquid exudate, the PRF serum. The question arises regarding how much the overall activity remains in the PRF membranes and what is discarded into the PRF serum. To this end, we have exposed gingival fibroblasts to lysates prepared from PRF membranes and PRF serum, followed by bulk RNA sequencing. A total of 268 up- and 136 down-regulated genes in gingival fibroblasts exposed to PRF membrane lysates were significantly regulated under the premise of a minimum log2 with 2.5-fold change and a minus log10 significance level of two, respectively. PRF serum only caused 62 up- and 32 down-regulated genes under these conditions. Among the 46 commonly up-regulated genes were CXCL1, CXCL5, CXCL6, CXCL8, IL33, IL6, and PTGS2/COX2, stanniocalcin-1—all linked to an inflammatory response. PRF membrane lysates further increased chemokines CCL2, CCL7, CXCL2, CXCL3, and IL1R1, IL1RL1, and IL1RN, as well as the paracrine factors IL11, LIF, IGF1, BMP2, BMP6, FGF2, and CCN2/CTGF, and all hyaluronan synthases. On the other hand, PRF serum increased DKK1. The genes commonly down-regulated by PRF membrane lysates and PRF serum included interferon-induced protein with tetratricopeptide repeats (IFIT1, IFIT2, IFIT3) and odd-skipped-related transcription factors (OSR1 and OSR2), as well as FGF18 and GDF15, respectively. Taken together, PRF membrane lysates, compared to PRF serum, cause a more complex response in gingival fibroblasts, but each increased chemokine expression in gingival fibroblasts. Full article
(This article belongs to the Special Issue Oral Tissue Stem Cells in Regenerative Dentistry)
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9 pages, 2415 KiB  
Article
Enhancing Dental Pulp Stem Cell Proliferation and Odontogenic Differentiation with Protein Phosphatase 1-Disrupting Peptide: An In Vitro Study
by Anna Kobrock, Bárbara Matos, Daniela Patrício, Liliana Grenho, John Howl, Margarida Fardilha and Pedro S. Gomes
Cells 2024, 13(13), 1143; https://doi.org/10.3390/cells13131143 - 3 Jul 2024
Viewed by 1026
Abstract
The reparative and regenerative capabilities of dental pulp stem cells (DPSCs) are crucial for responding to pulp injuries, with protein phosphatase 1 (PP1) playing a significant role in regulating cellular functions pertinent to tissue healing. Accordingly, this study aimed to explore the effects [...] Read more.
The reparative and regenerative capabilities of dental pulp stem cells (DPSCs) are crucial for responding to pulp injuries, with protein phosphatase 1 (PP1) playing a significant role in regulating cellular functions pertinent to tissue healing. Accordingly, this study aimed to explore the effects of a novel cell-penetrating peptide Modified Sperm Stop 1-MSS1, that disrupts PP1, on the proliferation and odontogenic differentiation of DPSCs. Employing MSS1 as a bioportide, DPSCs were cultured and characterized for metabolic activity, cell proliferation, and cell morphology alongside the odontogenic differentiation through gene expression and alkaline phosphatase (ALP) activity analysis. MSS1 exposure induced early DPSC proliferation, upregulated genes related to odontogenic differentiation, and increased ALP activity. Markers associated with early differentiation events were induced at early culture time points and those associated with matrix mineralization were upregulated at mid-culture stages. This investigation is the first to document the potential of a PP1-disrupting bioportide in modulating DPSC functionality, suggesting a promising avenue for enhancing dental tissue regeneration and repair. Full article
(This article belongs to the Special Issue Oral Tissue Stem Cells in Regenerative Dentistry)
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16 pages, 5168 KiB  
Article
Impact of Resolvin-E1 and Maresin-1 on Bone Marrow Stem Cell Osteogenesis under Inflammatory Stress
by Shahd AlZahrani, Zakia Shinwari, Ayodele Alaiya and Ahmed Al-Kahtani
Cells 2024, 13(11), 932; https://doi.org/10.3390/cells13110932 - 28 May 2024
Cited by 1 | Viewed by 1097
Abstract
Periodontal disease is characterized by inflammation and bone loss. Central to its pathogenesis is the dysregulated inflammatory response, complicating regenerative therapies. Mesenchymal stem cells (MSCs) hold significant promise in tissue repair and regeneration. This study investigated the effects of specialized pro-resolving mediators (SPMs), [...] Read more.
Periodontal disease is characterized by inflammation and bone loss. Central to its pathogenesis is the dysregulated inflammatory response, complicating regenerative therapies. Mesenchymal stem cells (MSCs) hold significant promise in tissue repair and regeneration. This study investigated the effects of specialized pro-resolving mediators (SPMs), Resolvin E1 (RvE1) and Maresin 1 (MaR1), on the osteogenic differentiation of human bone marrow-derived MSCs under inflammatory conditions. The stem cells were treated with SPMs in the presence of lipopolysaccharide (LPS) to simulate an inflammatory environment. Osteogenic differentiation was assessed through alkaline phosphatase activity and alizarin red staining. Proteomic analysis was conducted to characterize the protein expression profile changes, focusing on proteins related to osteogenesis and osteoclastogenesis. Treatment with RvE1 and MaR1, both individually and in combination, significantly enhanced calcified deposit formation. Proteomic analysis revealed the differential expression of proteins associated with osteogenesis and osteoclastogenesis, highlighting the modulatory impact of SPMs on bone metabolism. RvE1 and MaR1 promote osteogenic differentiation of hBMMSCs in an inflammatory environment, with their combined application yielding synergistic effects. This study provides insights into the therapeutic potential of SPMs in enhancing bone regeneration, suggesting a promising avenue for developing regenerative therapies for periodontal disease and other conditions characterized by inflammation-induced bone loss. Full article
(This article belongs to the Special Issue Oral Tissue Stem Cells in Regenerative Dentistry)
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18 pages, 4256 KiB  
Article
Dental Pulp Cell Transplantation Combined with Regenerative Endodontic Procedures Promotes Dentin Matrix Formation in Mature Mouse Molars
by Jorge Luis Montenegro Raudales, Yuta Okuwa and Masaki Honda
Cells 2024, 13(4), 348; https://doi.org/10.3390/cells13040348 - 16 Feb 2024
Viewed by 1762
Abstract
Regenerative endodontic procedures (REPs) are promising for dental pulp tissue regeneration; however, their application in permanent teeth remains challenging. We assessed the potential combination of an REP and local dental pulp cell (DPC) transplantation in the mature molars of C57BL/6 mice with (REP [...] Read more.
Regenerative endodontic procedures (REPs) are promising for dental pulp tissue regeneration; however, their application in permanent teeth remains challenging. We assessed the potential combination of an REP and local dental pulp cell (DPC) transplantation in the mature molars of C57BL/6 mice with (REP + DPC group) or without (REP group) transplantation of DPCs from green fluorescent protein (GFP) transgenic mice. After 4 weeks, the regenerated tissue was evaluated by micro-computed tomography and histological analyses to detect odontoblasts, vasculogenesis, and neurogenesis. DPCs were assessed for mesenchymal and pluripotency markers. Four weeks after the REP, the molars showed no signs of periapical lesions, and both the REP and REP + DPC groups exhibited a pulp-like tissue composed of a cellular matrix with vessels surrounded by an eosin-stained acellular matrix that resembled hard tissue. However, the REP + DPC group had a broader cellular matrix and uniquely contained odontoblast-like cells co-expressing GFP. Vasculogenesis and neurogenesis were detected in both groups, with the former being more prominent in the REP + DPC group. Overall, the REP was achieved in mature mouse molars and DPC transplantation improved the outcomes by inducing the formation of odontoblast-like cells and greater vasculogenesis. Full article
(This article belongs to the Special Issue Oral Tissue Stem Cells in Regenerative Dentistry)
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Review

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23 pages, 1003 KiB  
Review
The Genetic Aspects of Periodontitis Pathogenesis and the Regenerative Properties of Stem Cells
by Klaudia Ustianowska, Łukasz Ustianowski, Estera Bakinowska, Kajetan Kiełbowski, Joanna Szostak, Martyna Murawka, Bartosz Szostak and Andrzej Pawlik
Cells 2024, 13(2), 117; https://doi.org/10.3390/cells13020117 - 9 Jan 2024
Cited by 2 | Viewed by 2493
Abstract
Periodontitis (PD) is a prevalent and chronic inflammatory disease with a complex pathogenesis, and it is associated with the presence of specific pathogens, such as Porphyromonas gingivalis. Dysbiosis and dysregulated immune responses ultimately lead to chronic inflammation as well as tooth and [...] Read more.
Periodontitis (PD) is a prevalent and chronic inflammatory disease with a complex pathogenesis, and it is associated with the presence of specific pathogens, such as Porphyromonas gingivalis. Dysbiosis and dysregulated immune responses ultimately lead to chronic inflammation as well as tooth and alveolar bone loss. Multiple studies have demonstrated that genetic polymorphisms may increase the susceptibility to PD. Furthermore, gene expression is modulated by various epigenetic mechanisms, such as DNA methylation, histone modifications, or the activity of non-coding RNA. These processes can also be induced by PD-associated pathogens. In this review, we try to summarize the genetic processes that are implicated in the pathogenesis of PD. Furthermore, we discuss the use of these mechanisms in diagnosis and therapeutic purposes. Importantly, novel treatment methods that could promote tissue regeneration are greatly needed in PD. In this paper, we also demonstrate current evidence on the potential use of stem cells and extracellular vesicles to stimulate tissue regeneration and suppress inflammation. The understanding of the molecular mechanisms involved in the pathogenesis of PD, as well as the impact of PD-associated bacteria and stem cells in these processes, may enhance future research and ultimately improve long-term treatment outcomes. Full article
(This article belongs to the Special Issue Oral Tissue Stem Cells in Regenerative Dentistry)
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