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Stem Cell Therapy in Dentistry and Oral and Maxillofacial Abnormalities

Cover image for Research Topic "Stem Cell Therapy in Dentistry and Oral and Maxillofacial Abnormalities"
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Editorial06 September 2024
Editorial: Stem cell therapy in dentistry and oral and maxillofacial abnormalities
Ali Golchin, Ilya D. Klabukov, Yaşar Murat Elçinand Arash Khojasteh

experiencing a renaissance, driven by groundbreaking research that is pushing the boundaries of traditional treatments. Currently, cell technologies allow bridging the gap with the potential to revolutionize clinical practices and improve patient outcomes in dentistry, oral and maxillofacial surgery. However, several challenges still need to be addressed. It is crucial to consider the emerging obstacles associated with using stem cells in regenerative dentistry and to evaluate their effectiveness compared to traditional treatments. Over the past few decades, the rise of stem cell research, in conjunction with tissue engineering, has introduced new perspectives in regenerative medicine and, by extension, regenerative dentistry. As researchers look into different stem cell sources, especially those-derived oral tissues, and new ways to make scaffolds, like bio-printing, they are more likely to combine these advances to come up with new approaches to treat patients.However, the majority of emphasis has been directed into therapeutic treatments, while simultaneously, the majority of fundamental questions have been answered. This special issue aims to highlight recent research in the field of stem cell applications in dentistry and maxillofacial reconstruction.The influence of the immune system on tissue repair is still an understudied area of regenerative medicine. Liu et al. performed a review of the interactions between immune cells and stem cells, exploring their interaction and their involvement in jaw development, maintenance of homeostasis, and pathological circumstances [1]. The primary goal of the study was to ultimately explore the relationship between periodontal ligament stem cells, dental pulp mesenchymal stem cells, jawbone mesenchymal stem cells, and Schwann cells in the immune microenvironment of the jaw. A primary concern in the field of regenerative dentistry is the enhancement of odontogenesis by improving differentiation and proliferation of specific stem cells. In this regard, Inubushi et al.suggested enhancing dentin production in odontoblasts by utilizing a distinctive chlorinated oxidant known as Matching Transformation System ® (MA-T) [2]. They found that via activating the canonical Wnt signaling pathway, MA-T treatment in odontoblasts decreased the sulfation of HSPG and increased the levels of dentin sialophosphoprotein (Dspp) and Dentin Matrix Protein 1 (Dmp1). Furthermore, the use of MA-T treatments outside of the living organism enhanced the formation of dentin matrix in developing tooth samples. However, a comprehensive investigation is necessary to precisely determine the function of the intricate Wnt signaling network in dentin formation. Moreover, in vitro investigation shown that LiCl treatment increased the mRNA expression of Wnt10a and Wnt6 in odontoblasts, but had no effect on Wnt5a. Similarly, MA-T treatment at concentrations of 0.2 ppm and 1.0 ppm also had no effect on Wnt5a expression. The study utilized primary mouse dental papilla mesenchymal cells (mDP cells) to further examine the growth into odontoblasts, chondrocytes, and adipocytes. The study proposes a novel approach to stimulate dentin formation by modifying HSPG. It also elucidates the therapeutic processes of MA-T in promoting the differentiation of odontoblasts [2]. These findings suggest a promising potential for using pharmaceutical methods to regenerate dental tissues.In another study, Irfan et al. discovered that disabling the C5a-like receptor 2 (C5L2) CRISPR gene significantly improves the process of mineralization in TNFα-stimulated dental pulp stem cells (DPSCs), and promotes the production of dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 [3]. This study has attempted to clarify the function of inflammation in dentinogenesis in order to develop effective ways for engineering stem cell-based approaches [4].In a clinical study, Bouland et al. evaluated the capacity of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) to treat medication-related osteonecrosis of the jaw (MRONJ) [4]. As we know, the AT-SVF consists of mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC) that stimulate the growth of bone tissue. The L-PRF scaffold facilitates tissue repair by releasing growth factors. The study included nine individuals who had a total of ten MRONJ lesions, all of which showed no symptoms of recurrence. Three-dimensional medical imaging demonstrated bone regeneration six months post-surgery. The findings indicate a novel therapeutic strategy for MRONJ involving the use of autologous AT-SVF within an L-PRF scaffold [4].In addition to teeth and oral bones, other oral related diseases can be targeted for stem cell-based therapies. For instance, the salivary gland hypo-function (SGH) is a medical issue that results in dry mouth, heightened susceptibility to disorders, and diminished quality of life. Present therapies mostly aim to alleviate symptoms and enhance quality of life, but do not restore impaired glands.Pluripotent stem cells (PSCs) are being recognized as a promising treatment option for SGH. Song et al. reviewed the related preclinical studies and demonstrated that PSCs exhibit encouraging immunomodulatory and tissue regeneration properties for SGH [5]. This study provides a comprehensive analysis of the effectiveness and prospective application of PSCs in the treatment of SGH, which can serve as valuable guidance for future research endeavors [5].Overall, there is no doubt that regenerative dentistry will continue to rapidly advance and improve treatment methods as the convergence of disciplines continues, and stem cell-based approaches and tissue engineering continue to improve. These technological breakthroughs show significant potential for the future of dentistry and the treatment of oral and maxillofacial disorders, providing creative ways to progress this discipline.

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Treatment of medication-related osteonecrosis of the jaw with cell therapy
ORIGINAL RESEARCH
26 January 2024
Treatment of medication-related osteonecrosis of the jaw with cell therapy
Cyril Lucien Bouland, 14 more and Nathalie Meuleman
Introduction: Medication-related osteonecrosis of the jaw (MRONJ) poses a significant challenge considering the absence of a “gold standard” treatment. Cell-based therapy and tissue engineering offer promising therapeutic alternatives. This study aimed to harness the regenerative properties of adipose-tissue stromal vascular fraction (AT-SVF) and leukocyte-platelet-rich fibrin (L-PRF) for MRONJ treatment. AT-SVF contains mesenchymal stromal cells (MSC) and endothelial progenitor cells (EPC), which promote bone formation, while the L-PRF scaffold can serve as a three-dimensional scaffold for the AT-SVF and support tissue healing through growth factor release. Materials and Methods: The protocol involved applying autologous AT-SVF within an L-PRF matrix following surgical debridement. Age, gender, body mass index, comorbidities, underlying oncological condition, prescribed antiresorptive treatment: BP or DMB, antiresorptive treatment duration, antiresorptive treatment potential discontinuation, number of MRONJ lesion, MRONJ location, MRONJ stage, MRONJ trigger factor were assessed for each patient. Patients underwent the procedure and were monitored for a minimum of six months based on clinical, biological and medical imaging criteria. Results: Nine patients, with a total of ten MRONJ lesions, participated in the study. Six patients were female, and three were male, with a mean age of 68±8 years. Four patients had multiple myeloma (MM), three had metastatic breast cancer, and two had metastatic prostate cancer. Seven MRONJ cases were classified as stage II, and three were classified as stage III. Soft tissue completely healed within a month after treatment in nine cases, with no clinical improvement observed in the remaining case. During follow-up, no sign of MRONJ recurrence was observed. Tridimensional medical imaging revealed bone healing six months after the surgical procedure. Immunophenotyping confirmed the presence of MSC and EPC in the AT-SVF: 12,6±4,5% CD31+, 20.5±7,8% CD34+, 34,4±7,3% CD146+ and 54,6±7,4% CD45+. Conclusion: This prospective study introduces a potential new treatment approach for MRONJ using autologous AT-SVF within an L-PRF scaffold. Our results are encouraging and suggest the need for further investigation with a larger patient cohort to better understand the underlying mechanisms.

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13 citations

Dental caries is one of the most common human pathological conditions resulting from the invasion of bacteria into the dentin. Current treatment options are limited. In many cases, the endodontic therapy leads to permanent pulp tissue loss. Dentin-pulp complex regeneration involves dental pulp stem cells (DPSCs) that differentiate into odontoblast-like cells under an inflammatory context. However, limited information is available on how DPSC differentiation processes are affected under inflammatory environments. We have identified the crucial role of complement C5a and its receptor C5aR in the inflammation induced odontoblastic DPSC differentiation. Here, we further investigated the role of a second and controversial C5a receptor, C5L2 in this process and explored the underlying mechanism. Human DPSCs were examined during 7, 10, and 14-day odontogenic differentiation treated with TNFα, C5L2 CRISPR, and tyrosine receptor kinase B (TrkB) antagonist (Cyclotraxin B; CTX-B). Our data demonstrate that C5L2 CRISPR Knock-out (KO) enhances mineralization in TNFα-stimulated differentiating DPSCs. We further confirmed that C5L2 CRISPR KO significantly enhances dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) expression after 14-day odontoblastic DPSC differentiation and treatment with CTX-B abolished the TNFα/C5L2 CRISPR KO-induced DSPP and DMP-1 increase suggesting the TrkB`s critical role in this process. Our data suggest a regulatory role of C5L2 and TrkB in the TNFα-induced odontogenic DPSCs differentiation. This study may provide a useful tool to understand the mechanisms of the role of inflammation in dentinogenesis that is required for successful DPSC engineering strategies.

3,703 views

13 citations

Salivary gland hypofunction (SGH) caused by systemic disease, drugs, aging, and radiotherapy for head and neck cancer can cause dry mouth, which increases the risk of disorders such as periodontitis, taste disorders, pain and burning sensations in the mouth, dental caries, and dramatically reduces the quality of life of patients. To date, the treatment of SGH is still aimed at relieving patients' clinical symptoms and improving their quality of life, and is not able to repair and regenerate the damaged salivary glands. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and expanded pluripotent stem cells (EPSCs), are an emerging source of cellular therapies that are capable of unlimited proliferation and differentiation into cells of all three germ layers. In recent years, the immunomodulatory and tissue regenerative effects of PSCs, their derived cells, and paracrine products of these cells have received increasing attention and have demonstrated promising therapeutic effects in some preclinical studies targeting SGH. This review outlined the etiologies and available treatments for SGH. The existing efficacy and potential role of PSCs, their derived cells and paracrine products of these cells for SGH are summarized, with a focus on PSC-derived salivary gland stem/progenitor cells (SGS/PCs) and PSC-derived mesenchymal stem cells (MSCs). In this Review, we provide a conceptual outline of our current understanding of PSCs- based therapy and its importance in SGH treatment, which may inform and serve the design of future studies.

8,919 views

17 citations

ORIGINAL RESEARCH
26 October 2023
On-demand chlorine dioxide solution enhances odontoblast differentiation through desulfation of cell surface heparan sulfate proteoglycan and subsequent activation of canonical Wnt signaling
Toshihiro Inubushi, 8 more and Takashi Yamashiro

3,919 views

2 citations