Vol 19, No 4 (2024)

Medicine

Emerging Role of miRNAs in the Pathogenesis of Periodontitis

Taheri M., Khoshbakht T., Hussen B., Abdullah S., Ghafouri-Fard S., Sayad A.

Abstract

MicroRNAs (miRNAs) have been found to participate in the pathogenesis of several immune-related conditions through the modulation of the expression of cytokine coding genes and other molecules that affect the activity of the immune system. Periodontitis is an example of these conditions associated with the dysregulation of several miRNAs. Several miRNAs such as let-7 family, miR-125, miR-378, miR-543, miR-302, miR-214, miR-200, miR-146, miR-142, miR-30 and miR-21 have been shown to be dysregulated in patients with periodontitis. miR-146 is the most assessed miRNA in these patients, which is up-regulated in most studies in patients with periodontitis. In the present review, we describe the impact of miRNAs dysregulation on the pathoetiology of periodontitis.

Current Stem Cell Research & Therapy. 2024;19(4):427-448
pages 427-448 views

Bone Scaffold Materials in Periodontal and Tooth-supporting Tissue Regeneration: A Review

Jahangirnezhad M., Mahmoudinezhad S., Moradi M., Moradi K., Rohani A., Tayebi L.

Abstract

Background and Objectives:Periodontium is an important tooth-supporting tissue composed of both hard (alveolar bone and cementum) and soft (gingival and periodontal ligament) sections. Due to the multi-tissue architecture of periodontium, reconstruction of each part can be influenced by others. This review focuses on the bone section of the periodontium and presents the materials used in tissue engineering scaffolds for its reconstruction.

Materials and Methods:The following databases (2015 to 2021) were electronically searched: ProQuest, EMBASE, SciFinder, MRS Online Proceedings Library, Medline, and Compendex. The search was limited to English-language publications and in vivo studies.

Results:Eighty-three articles were found in primary searching. After applying the inclusion criteria, seventeen articles were incorporated into this study.

Conclusions:In complex periodontal defects, various types of scaffolds, including multilayered ones, have been used for the functional reconstruction of different parts of periodontium. While there are some multilayered scaffolds designed to regenerate alveolar bone/periodontal ligament/cementum tissues of periodontium in a hierarchically organized construct, no scaffold could so far consider all four tissues involved in a complete periodontal defect. The progress and material considerations in the regeneration of the bony part of periodontium are presented in this work to help investigators develop tissue engineering scaffolds suitable for complete periodontal regeneration.

Current Stem Cell Research & Therapy. 2024;19(4):449-460
pages 449-460 views

Application of CAD-CAM Technologies for Maxillofacial Bone Regeneration: A Narrative Review of the Clinical Studies

Boroojeni H.S., Mohaghegh S., Khojasteh A.

Abstract

The application of regenerative methods in treating maxillofacial defects can be categorized as functional bone regeneration in which scaffolds without protection are used and in-situ bone regeneration in which a protected healing space is created to induce bone formation. It has been shown that functional bone regeneration can reduce surgical time and obviate the necessity of autogenous bone grafting. However, studies mainly focused on applying this method to reconstruct minor bone effects, and more investigation concerning the large defects is required. In terms of in situ maxillofacial bone regeneration with the help of CAD-CAM technologies, the present data have suggested feasible mesh rigidity, perseverance of the underlying space, and apt augmentative results with CAD-CAM-based individualized Ti meshes. However, complications, including dehiscence and mesh exposure, coupled with consequent graft loss, infection and impeded regenerative rates have also been reported

Current Stem Cell Research & Therapy. 2024;19(4):461-472
pages 461-472 views

Current Trends, Advances, and Challenges of Tissue Engineering-Based Approaches of Tooth Regeneration: A Review of the Literature

Hazrati P., Mirtaleb M., Boroojeni H., Koma A., Nokhbatolfoghahaei H.

Abstract

Introduction:Tooth loss is a significant health issue. Currently, this situation is often treated with the use of synthetic materials such as implants and prostheses. However, these treatment modalities do not fully meet patients' biological and mechanical needs and have limited longevity. Regenerative medicine focuses on the restoration of patients' natural tissues via tissue engineering techniques instead of rehabilitating with artificial appliances. Therefore, a tissue-engineered tooth regeneration strategy seems like a promising option to treat tooth loss.

Objective:This review aims to demonstrate recent advances in tooth regeneration strategies and discoveries about underlying mechanisms and pathways of tooth formation

Results and Discussion:Whole tooth regeneration, tooth root formation, and dentin-pulp organoid generation have been achieved by using different seed cells and various materials for scaffold production. Bioactive agents are critical elements for the induction of cells into odontoblast or ameloblast lineage. Some substantial pathways enrolled in tooth development have been figured out, helping researchers design their experiments more effectively and aligned with the natural process of tooth formation.

Conclusion:According to current knowledge, tooth regeneration is possible in case of proper selection of stem cells, appropriate design and manufacturing of a biocompatible scaffold, and meticulous application of bioactive agents for odontogenic induction. Understanding innate odontogenesis pathways play a crucial role in accurately planning regenerative therapeutic interventions in order to reproduce teeth.

Current Stem Cell Research & Therapy. 2024;19(4):473-496
pages 473-496 views

Comparison of Periodontal Ligament Stem Cells with Mesenchymal Stem Cells from Other Sources: A Scoping Systematic Review of In vitro and In vivo Studies

Kadkhoda Z., Motie P., Rad M., Mohaghegh S., Kouhestani F., Motamedian S.

Abstract

Objective:The application of stem cells in regenerative medicine depends on their biological properties. This scoping review aimed to compare the features of periodontal ligament stem cells (PDLSSCs) with stem cells derived from other sources.

Design:An electronic search in PubMed/Medline, Embase, Scopus, Google Scholar and Science Direct was conducted to identify in vitro and in vivo studies limited to English language.

Results:Overall, 65 articles were included. Most comparisons were made between bone marrow stem cells (BMSCs) and PDLSCs. BMSCs were found to have lower proliferation and higher osteogenesis potential in vitro and in vivo than PDLSCs; on the contrary, dental follicle stem cells and umbilical cord mesenchymal stem cells (UCMSCs) had a higher proliferative ability and lower osteogenesis than PDLSCs. Moreover, UCMSCs exhibited a higher apoptotic rate, hTERT expression, and relative telomerase length. The immunomodulatory function of adipose-derived stem cells and BMSCs was comparable to PDLSCs. Gingival mesenchymal stem cells showed less sensitivity to long-term culture. Both pure and mixed gingival cells had lower osteogenic ability compared to PDLSCs. Comparison of dental pulp stem cells (DPSCs) with PDLSCs regarding proliferation rate, osteo/adipogenesis, and immunomodulatory properties was contradictory; however, in vivo bone formation of DPSCs seemed to be lower than PDLSCs.

Conclusion:In light of the performed comparative studies, PDLSCs showed comparable results to stem cells derived from other sources; however, further in vivo studies are needed to determine the actual pros and cons of stem cells in comparison to each other.

Current Stem Cell Research & Therapy. 2024;19(4):497-522
pages 497-522 views

Effects of Growth Factors on the Differentiation of Dental Stem Cells: A Systematic Review and Meta-analysis (Part I)

Shamszadeh S., Shirvani A., Torabzadeh H., Asgary S.

Abstract

Introduction:To evaluate the biological interaction between dental stem cells (DSCs) and different growth factors in the field of regenerative endodontics.

Methods:A systematic search was conducted in the electronic databases up to October 2021. This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Ex vivo studies evaluating the biological interactions of DSCs and growth factors were included. The meta-analysis was performed according to the type of growth factor. The outcomes were cell viability/ proliferation and mineralization. Standardized mean differences (SMDs) were estimated using the random-effect maximum-likelihood method (P < .05). Additional analysis was performed to find any potential source of heterogeneity.

Results:Twenty articles were included in the systematic review; meta-analysis was performed for fibroblast growth factor-2 (FGF-2) and Transforming growth factor-ß1 (TGF-β1) (n = 5). Results showed that use of FGF-2 significantly increased cell proliferation on day 1-(SMD = 3.56, P = 0.00), 3-(SMD = 9.04, P = 0.00), 5-(SMD = 8.37, P = 0.01), and 7 (SMD=8.51, P=0.00) than the control group. TGF-ß1 increased alkaline phosphatase (ALP) activity more than control only on day 3 (SMD = 3.68, P = 0.02). TGF-β1 had no significant effect on cell proliferation on days 1 and 3 (P > 0.05) and on ALP activity on days 5 and 7 (P > 0.05). Meta-regression analysis showed that different covariates (i.e., cell type, passage number, and growth factors' concentration) could significantly influence the effect sizes at different follow- ups (p < 0.05).

Conclusion:Specific growth factors might enhance the proliferation and mineralization of DSCs; however, the obtained evidence was weak. Due to the high heterogeneity among the included studies, other growth factors' inhibitory/stimulatory effects on DSCs could not be evaluated.

Current Stem Cell Research & Therapy. 2024;19(4):523-543
pages 523-543 views

Photobiomodulation Effects on Periodontal Ligament Stem Cells: A Systematic Review of In Vitro Studies

Mylona V., Anagnostaki E., Chiniforush N., Barikani H., Lynch E., Grootveld M.

Abstract

Background:Stem cell therapy has been considered to play a paramount role in the treatment modalities available for regenerative dentistry. The established beneficial effects of photobiomodulation (PBM) at the cellular level have led to the combined use of these two factors (PBM and stem cells). The main goal of this study was firstly to critically appraise the effects of PBM on periodontal ligament stem cells (PDLSCs), and secondly to explore the most effective PBM protocols applied.

Methods:Pubmed, Cochrane, Scopus, Science Direct, and Google Scholar search engines were used to identify experimental in vitro studies in which PBM was applied to cultured PDLSCs. After applying specific keywords, additional filters, and inclusion/exclusion criteria, a preliminary number of 245 articles were narrowed down to 11 in which lasers and LEDs were used within the 630 - 1064 nm wavelength range. Selected articles were further assessed by three independent reviewers for strict compliance with PRISMA guidelines, and a modified Cochrane risk of bias to determine eligibility.

Statistical Analysis:The dataset analysed was extracted from the studies with sufficient and clearly presented PBM protocols. Simple univariate regression analysis was performed to explore the significance of contributions of potential quantitative predictor variables toward study outcomes, and a one-way ANOVA model was employed for testing differences between the laser or LED sources of the treatments. The significance level for testing was set at α = 0.05.

Results:The proliferation rate, osteogenic differentiation, and expression of different indicative genes for osteogenesis and inflammation suppression were found to be positively affected by the application of various types of lasers and LEDs. With regard to the PBM protocol, only the wavelength variable appeared to affect the treatment outcome; indeed, the 940 nm wavelength parameter was found not to exert a favourable effect.

Conclusions:Photobiomodulation can enhance the stemness and differentiation capacities of periodontal ligament stem cells. Therefore, for PBM protocols, there remains no consensus amongst the scientific community. Statistical analyses performed here indicated that the employment of a near-infrared (NIR) wavelength of 940 nm may not yield a significant favourable outcome, although those within the 630 - 830 nm range did so. Concerning the fluence, it should not exceed 8 J/cm2 when therapy is applied by LED devices, and 4 J/cm2 when applied by lasers, respectively.

Current Stem Cell Research & Therapy. 2024;19(4):544-558
pages 544-558 views

The Role of Photobiomodulation on Dental-Derived Stem Cells in Regenerative Dentistry: A Comprehensive Systematic Review

Firoozi P., Amiri M.A., Soghli N., Farshidfar N., Hakimiha N., Fekrazad R.

Abstract

Background:Photobiomodulation therapy involves exposing tissues to light sources, including light-emitting diodes or low-level lasers, which results in cellular function modulation. The molecular mechanism of this treatment is revealed, demonstrating that depending on the light settings utilized, it has the potential to elicit both stimulatory and inhibitory reactions.

Objective:The current systematic review aimed to evaluate the impact of photobiomodulation therapy on dental stem cells and provide an evidence-based conclusion in this regard.

Methods:This systematic review was performed and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) revised guidelines. PICO(S) components were employed to define the inclusion criteria. Web of Science, Scopus, Medline as well as grey literature, and google scholar were searched up to September 2021 to retrieve relevant papers.

Results:Photobiomodulation therapy showed promising effects on the proliferation, viability, and differentiation of dental stem cells. This finding was based on reviewing related articles with a low risk of bias.

Conclusion:Despite the positive benefits of photobiomodulation therapy on dental stem cells, the current data do not provide a definitive conclusion on the best physical parameters for enhancing cell viability, proliferation, and differentiation.

Current Stem Cell Research & Therapy. 2024;19(4):559-586
pages 559-586 views

The Role of Growth Factor Delivery Systems on Cellular Activities of Dental Stem Cells: A Systematic Review (Part II)

Shamszadeh S., Shirvani A., Asgary S.

Abstract

Objective:The current systematic review aims to provide the available ex vivo evidence evaluating the biological interactions of dental stem cells (DSCs) and growth factor delivery systems.

Methods:Following the Preferred Reporting Items for a Systematic Reviews and Meta-Analyses (PRISMA) guidelines, systematic search was conducted in the electronic databases (PubMed/Medline, Scopus, Web of Science, and Google Scholar) up to January 2022. Studies evaluating the biological interactions of DSCs and growth factor delivery systems were included. The outcome measures were cell cytocompatibility, mineralization, and differentiation.

Results:Sixteen studies were selected for the qualitative synthesis. The following growth factor delivery systems exhibit adequate cytocompatibility, enhanced mineralization, and osteo/odontoblast differentiation potential of DSCs: 1) Fibroblast growth factor (FGF-2)-loaded-microsphere and silk fibroin, 2) Bone morphogenic protein-2 (BMP-2)-loaded-microsphere and mesoporous calcium silicate scaffold, 3) Transforming growth factor Beta 1 (TGF-ß1)-loaded-microsphere, glass ionomer cement (GIC), Bio-GIC and liposome, 4) TGF-ß1-loaded-nanoparticles/scaffold, 5) Vascular endothelial growth factor (VEGF)-loaded-fiber and hydrogel, 6) TGF-ß1/VEGF-loaded-nanocrystalline calcium sulfate/hydroxyapatite/calcium sulfate, 7) Epidermal growth factor-loaded- nanosphere, 8) Stem cell factor/DSCs-loaded-hydrogel and Silk fibroin, 9) VEGF/BMP-2/DSCs-loaded-Three-dimensional matrix, 10) VEGF/DSCs-loaded-microsphere/hydrogel, and 11) BMP-2/DSCs and VEGF/DSCs-loaded-Collagen matrices. The included delivery systems showed viability, except for Bio-GIC on day 3. The choice of specific growth factors and delivery systems (i.e., BMP-2-loaded-microsphere and VEGF-loaded-hydrogel) resulted in a greater gene expression.

Conclusions:This study, with low-level evidence obtained from ex vivo studies, suggests that growth factor delivery systems induce cell proliferation, mineralization, and differentiation toward a therapeutic potential in regenerative endodontics.

Current Stem Cell Research & Therapy. 2024;19(4):587-610
pages 587-610 views

Clinical, Radiographic, and Histologic Outcomes of Regenerative Endodontic Treatment in Human Immature Teeth Using Different Biological Scaffolds: A Systematic Review and Meta-analysis

Vatankhah M., Najary S., Dianat O.

Abstract

Background:Biological scaffolds such as blood clot (BC), platelet-rich plasma (PRP), platelet- rich fibrin (PRF), and platelet pellet (PP) are used in regenerative endodontic treatments (RETs).

Objective:To systematically and quantitatively evaluate clinical, radiographic, and histologic outcomes of RET studies using different biological scaffolds.

Methods:MEDLINE, Scopus, Cochrane library, and Embase were searched to identify studies on RET procedures with any scaffold type performed on immature non-vital human teeth, employing any type of biological scaffold. Clinical, radiographic, and histologic outcomes were extracted. Cochrane collaboration risk of bias tool and Newcastle–Ottawa scale were used for quality assessment. Random and fixed model meta-analysis was carried out with 95% confidence interval.

Results:Thirty-two studies were included in the qualitative analysis from the primarily retrieved 1895 studies. Only one study had high risk of bias and 71.8% of the studies had high quality. None of the studies reported any histologic findings. Thirty studies were included in meta-analysis. Clinical success rate of RET using either BC, PRP, or PRF was >99%. Furthermore, 32%, 23%, and 27% of BC, PRP, and PRF cases regained vitality, respectively. Periapical healing was seen in 67%, 75%, and 100% of BC, PRP, and PRF cases, respectively. There was no statistical difference between BC, PRP, or PRF regarding clinical success or any radiographic outcomes.

Conclusion:There was no significant difference between BC, PRP, and PRF in terms of clinical and radiographic outcomes. When it is difficult or dangerous to induce bleeding in root canals, PRP and PRF may be employed instead.

Current Stem Cell Research & Therapy. 2024;19(4):611-627
pages 611-627 views