Ian Ellis

Marco Tatullo

Mohammad Islam

Frontiers in Cell and Developmental Biology

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Editorial: Tissue regenerationusing dental stem cellsMarco Tatullo1,2,3*, Ian Ellis2 and Mohammad Islam2*1Department of Translational Biomedicine and Neuroscience (DIBRAIN), University of Bari Aldo Moro,Bari, Italy, 2School of Dentistry, University of Dundee, Dundee, United Kingdom, 3MIRROR—MedicalInstitute for Regeneration and Repairing and Organ Replacement, Interdepartmental Center, Universityof Bari Aldo Moro, Bari, ItalyKEYWORDStissue regeneration, dental stem cells (DSCs), biomaterial, growth factors, boneregenaration, immunomodulationEditorial on the Research TopicTissue regeneration using dental stem cellsTissue regeneration is a multidisciplinary field that combines various aspects of biology,medicine, materials science, and engineering. The three main pillars of tissue engineeringare: biomimetic biomaterials, growth factors able to drive cell fate, and, most importantly,stem cells. The complex interaction between resident stem cells and the local environment isa multifactorial process, regulated by multiple pathways able to actively influence a widerange of biological processes, from cell division to multilineage differentiation (Santilliet al.).In this landscape, several studies have undoubtedly demonstrated that dental andperiodontal tissues contain a significant amount of highly immature mesenchymal stemcells (MSCs). Dental MSCs (DMSCs) have been found in various dental tissues; moreover,DMSCs have gained growing interest from the scientific community because of their easyaccessibility, and thanks to their high strategic plasticity both in dental tissues repair and inregenerating several types of human tissues, including bone, cartilage, muscle, and neuraltissue. Despite oral tissues not being the most used niches of MSCs, we should carefullyrethink the role of DMSCs in tissue regeneration, as their use may lead to a significantadvance of knowledge in regenerative dentistry, impacting on the future treatments ofvarious systemic diseases (Namjoynik et al., 2023; Tatullo et al., 2023).This Research Topic has investigated a wide range of Research Topic, confirming thevaluable potentialities of DMSCs in tissue regeneration. Several approaches have beenproposed to optimize and enhance the regenerative potential of MSC, such as the use ofmedia conditioned with different growth factors, or cytokines and bioactive molecules (Liuet al., 2022; Ueda et al., 2022). However, these biological strategies alone were deemed not tohave reached their potential in some specific clinical conditions (Chouaib et al., 2022); thus,the researchers have added physical factors to improve cell proliferation. Using this premise,studies on various light sources, including LASERs and light-emitting diode (LED), werereviewed, and indicated that photo-biomodulation could be a good aid in those regenerativeprotocols aimed at stimulating periodontal ligament stem cells (PDLSCs) to repair damageddental tissues. However, the review revealed that there were a lot of ambiguity in theseprotocols and could have a conflict of interests as they were funded by the LASERcompanies (Ponnaiyan et al.).OPEN ACCESSEDITED AND REVIEWED BYAtsushi Asakura,University of Minnesota Twin Cities,United States*CORRESPONDENCEMarco Tatullo,marco.tatullo@uniba.itMohammad Islam,m.r.y.islam@dundee.ac.ukRECEIVED 15 March 2024ACCEPTED 15 March 2024PUBLISHED 22 March 2024CITATIONTatullo M, Ellis I and Islam M (2024), Editorial:Tissue regeneration using dental stem cells.Front. Cell Dev. Biol. 12:1401476.doi: 10.3389/fcell.2024.1401476COPYRIGHT© 2024 Tatullo, Ellis and Islam. This is an open-access article distributed under the terms of theCreative Commons Attribution License (CC BY).The use, distribution or reproduction in otherforums is permitted, provided the originalauthor(s) and the copyright owner(s) arecredited and that the original publication in thisjournal is cited, in accordance with acceptedacademic practice. No use, distribution orreproduction is permitted which does notcomply with these terms.Frontiers in Cell and Developmental Biology frontiersin.org01TYPE EditorialPUBLISHED 22 March 2024DOI 10.3389/fcell.2024.1401476Another important Research Topic discussed here is theimportance of bioactive scaffolds, as they can create an optimalmicroenvironment for MSCs. In fact, biomaterials, such aspolymers, hydrogels, or composites, are well known and safelyused in the production of scaffolds to be characterized by 3Dsuperficial morphology that should emphasize the concept of“sensing surface.” This concept, for example, may involve thepresence of a superficial presence of porosity with specific sizethat promote the MSCs adhesion, growth, and differentiation.Moreover, biomaterials need to contain specific molecules orfactors that mimic the target tissue microenvironments, topromote a targeted tissue regeneration (Gaharwar et al., 2020).Recently, biomaterials from foods or plants have been studied.Due to its mechanical properties, absence of any cell toxicity, andcapacity to create three-dimensional structures, chitin provides anoptimal environment for promoting stem cell viability, proliferation,and differentiation (Duminis et al., 2023). For the first time,Zawadzka-Knefel et al. investigated the biological responses ofhuman dental pulp stem cells (DPSCs) on purified 3D chitin-based scaffolds: these scaffolds were obtained from the marinedemosponge Aplysina fistularis and were then modified usinghydroxyapatite (HAp). The authors demonstrated that the chitin-based scaffolds, especially those modified with HAp, have thepotential of improve DPSCs adhesion and differentiation towardsosteoblasts and odontoblasts.The bone morphogenetic proteins (BMPs) are recognised asamong the most important players in many processes related to theformation and maintenance of various tissues, including bone,cartilage, and muscle (Akiyama et al., 2023). In addition, BMPshold significant potential as bioactive factors for tooth rootregeneration for regulating signalling pathways in various stagesof tooth root development. In particular, BMPs promote theformation of Hertwig’s epithelial root sheath (HERS) and thedifferentiation of DMSCs into odontoblasts, cementoblasts, andosteocytes, contributing to the formation of dentin andperiodontal tissues (Liu et al.).While BMPs play an important role in cell crosstalk, the role ofplasma membrane lipids is particularly important in cell division, asthey can influence the multilineage differentiation ability. The small,heterogeneous, and highly dynamic lipid domains in the cellmembranes, called lipid rafts, are involved in a variety of cellularprocesses, including receptor-mediated signal transduction, andthey can effectively regulate cellular signalling, includingproliferation, differentiation, apoptosis, autophagy, necrosis, stressresponses, inflammation, and senescence (Santilli et al.). Moreover,recent evidence has also shown that lipid rafts are involved in thesurvival, death, and metastasis of cancer cells, making them apromising target for cancer therapy (Li et al., 2022).It is well known that controlling and eliminating inflammation,and modulating immunity, may increase tissue regeneration. Aswidely reported in the literature, DMSCs can exhibit anti-inflammatory and immunomodulatory potential, making thempromising candidates for treating many inflammatory andautoimmune diseases (Li et al.). As happens with other stemcells, the immunomodulatory potential of DMSCs is regulated bythe release of molecules and factors in the extracellular environmentthrough specific carriers, such as extracellular vesicles (EVs) orexosomes (EXOs). Interestingly, EVs may play a pivotal role instem cell-based therapies (Codispoti et al., 2018), even if, the releaseof EVs, is susceptible to the lipid rafts’ perturbations (Feng et al.,2020). In this context, Tian et al. (2023) have demonstrated that EVsderived from hypoxic pre-conditioned DPSCs seems to ameliorateinflammatory-related osteolysis, through an intense modulation ofmacrophage polarisation, and an inhibition of osteoclastogenesisobtained by targeting Nuclear Factor Kappa B Subunit 1 (NF-kB1)which plays a crucial role in the inflammatory response andosteoclast formation.In conclusion, these studies have essentially confirmed thein vitro close interaction between DMSCs and several factors thathave different roles in tissue regeneration. It would also be strategicto investigate the regulatory mechanisms that are able to influenceDMSCs behaviour, for a better safety profile in their futureapplications on patients. In fact, although DMSCs have beenshown to have important pros, undoubtedly, important ResearchTopic such as safety remain. Thus, the future studies should focus ontheir safe and predictable use in daily surgical therapies, firstly indental regeneration, and then in systemic degenerative diseases.Author contributionsMT:Writing–original draft. IE: Writing–review and editing. MI:Writing–review and editing.FundingThe author(s) declare that no financial support was received forthe research, authorship, and/or publication of this article.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of the authorsand do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.Frontiers in Cell and Developmental Biology frontiersin.org02Tatullo et al. 10.3389/fcell.2024.1401476ReferencesAkiyama, T., Raftery, L. A., and Wharton, K. A. (2023). Bone morphogenetic proteinsignaling: the pathway and its regulation.Genetics 226 (2), iyad200. doi:10.1093/genetics/iyad200Chouaib, B., Cuisinier, F., and Collart-Dutilleul, P. Y. (2022). Dental stem cell-conditioned medium for tissue regeneration: optimization of production and storage.World J. Stem Cells 14 (4), 287–302. doi:10.4252/wjsc.v14.i4.287Codispoti, B., Marrelli, M., Paduano, F., and Tatullo, M. (2018). NANOmetric BIO-banked MSC-derived exosome (NANOBIOME) as a novel approach to regenerativemedicine. J. Clin. Med. 7 (10), 357. doi:10.3390/jcm7100357Duminis, T., Heljak, M., Święszkowski, W., Ereskovsky, A., Dziedzic, I., Nowicki, M.,et al. (2023). On the mechanical properties of microfibre-based 3D chitinous scaffoldsfrom selected verongiida sponges. Mar. Drugs 21 (9), 463. doi:10.3390/md21090463Feng, R., Ullah, M., Chen, K., Ali, Q., Lin, Y., and Sun, Z. (2020). Stem cell-derivedextracellular vesicles mitigate ageing-associated arterial stiffness and hypertension.J. Extracell. Vesicles 9 (1), 1783869. doi:10.1080/20013078.2020.1783869Gaharwar, A. K., Singh, I., and Khademhosseini, A. (2020). Engineered biomaterials for insitu tissue regeneration. Nat. Rev. Mater. 5 (9), 686–705. doi:10.1038/s41578-020-0209-xLi, B., Qin, Y., Yu, X., Xu, X., and Yu, W. (2022). Lipid raft involvement in signaltransduction in cancer cell survival, cell death and metastasis. Cell Prolif. 55 (1), e13167.doi:10.1111/cpr.13167Liu, Y., Kano, F., Hashimoto, N., Xia, L., Zhou, Q., Feng, X., et al. (2022).Determination of HMGB1 in hepatitis B virus-related acute-on-chronic liver failurepatients with acute kidney injury: early prediction and prognostic implications. Front.Pharmacol. 13, 1031790. doi:10.3389/fphar.2022.1031790Namjoynik, A., Islam, M. A., and Islam, M. (2023). Evaluating the efficacy of humandental pulp stem cells and scaffold combination for bone regeneration in animal models:a systematic review and meta-analysis. Stem Cell Res. Ther. 14 (1), 132. doi:10.1186/s13287-023-03357-wTatullo, M., Rengo, S., Sammartino, G., and Marenzi, G. (2023). Unlocking thepotential of dental-derived mesenchymal stem cells in regenerative medicine. J. Clin.Med. 12 (11), 3804. doi:10.3390/jcm12113804Tian, J., Chen, W., Xiong, Y., Li, Q., Kong, S., Li, M., et al. (2023). Smallextracellular vesicles derived from hypoxic preconditioned dental pulp stem cellsameliorate inflammatory osteolysis by modulating macrophage polarization andosteoclastogenesis. Bioact. Mater. 22, 326–342. doi:10.1016/j.bioactmat.2022.10.001Ueda, T., Ito, T., Inden, M., Kurita, H., Yamamoto, A., and Hozumi, I. (2022). Stemcells from human exfoliated deciduous teeth-conditioned medium (SHED-CM) is apromising treatment for amyotrophic lateral sclerosis. Front. Pharmacol. 13, 805379.doi:10.3389/fphar.2022.805379Frontiers in Cell and Developmental Biology frontiersin.org03Tatullo et al. 10.3389/fcell.2024.1401476

Editorial: Tissue regeneration using dental stem cells

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Editorial: Tissue regeneration using dental stem cells

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