Restorative Dentistry & Endodontics

Review Article

Stem cell-derived exosomes for dentin-pulp complex regeneration: a mini-review: Dina A. Hammouda, Alaa M Mansour, Mahmoud A. Saeed, Ahmed R. Zaher, Mohammed E. Grawish; Restor Dent Endod 2023;48(2):e20. Published online May 3, 2023; DOI: https://doi.org/10.5395/rde.2023.48.e20

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp–like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

Citations

Citations to this article as recorded by

Cell Homing Strategies in Regenerative Endodontic Therapy
David Kim, Sahng G. Kim
Cells.2025; 14(3): 201. CrossRef
Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy
Qingyue Kong, Yujie Wang, Nan Jiang, Yifan Wang, Rui Wang, Xiaohan Hu, Jing Mao, Xin Shi
Biomolecules.2024; 14(3): 330. CrossRef
Role and Molecular Mechanism of miR-586 in the Differentiation of Dental Pulp Stem Cells into Odontoblast-like Cells
Gang Pan, Qianwen Zhou, Chenhua Pan, Yingxue Zhang
Cell Biochemistry and Biophysics.2024; 83(1): 507. CrossRef

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Research Articles

Bioactivity of endodontic biomaterials on dental pulp stem cells through dentin: Bahar Javid, Narges Panahandeh, Hassan Torabzadeh, Hamid Nazarian, Ardavan Parhizkar, Saeed Asgary; Restor Dent Endod 2020;45(1):e3. Published online November 4, 2019; DOI: https://doi.org/10.5395/rde.2020.45.e3

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Objectives

This study investigated the indirect effect of calcium-enriched mixture (CEM) cement and mineral trioxide aggregate (MTA), as 2 calcium silicate-based hydraulic cements, on human dental pulp stem cells (hDPSCs) through different dentin thicknesses.

Materials and Methods

Two-chamber setups were designed to simulate indirect pulp capping (IPC). Human molars were sectioned to obtain 0.1-, 0.3-, and 0.5-mm-thick dentin discs, which were placed between the 2 chambers to simulate an IPC procedure. Then, MTA and CEM were applied on one side of the discs, while hDPSCs were cultured on the other side. After 2 weeks of incubation, the cells were removed, and cell proliferation, morphology, and attachment to the discs were evaluated under scanning electron microscopy (SEM). Energy-dispersive X-ray (EDXA) spectroscopy was performed for elemental analysis. Alkaline phosphatase (ALP) activity was assessed quantitatively. The data were analyzed using the Kruskal-Wallis and Mann-Whitney tests.

Results

SEM micrographs revealed elongated cells, collagen fibers, and calcified nucleations in all samples. EDXA verified that the calcified nucleations consisted of calcium phosphate. The largest calcifications were seen in the 0.1-mm-thick dentin subgroups. There was no significant difference in ALP activity across the CEM subgroups; however, ALP activity was significantly lower in the 0.1-mm-thick dentin subgroup than in the other MTA subgroups (p < 0.05).

Conclusions

The employed capping biomaterials exerted biological activity on hDPSCs, as shown by cell proliferation, morphology, and attachment and calcific precipitations, through 0.1- to 0.5-mm-thick layers of dentin. In IPC, the bioactivity of these endodontic biomaterials is probably beneficial.

Citations

Citations to this article as recorded by

Effect of pulp capping materials on odontogenic differentiation of human dental pulp stem cells: An in vitro study
Mahmoud M. Bakr, Mohamed Shamel, Shereen N. Raafat, Robert M. Love, Mahmoud M. Al‐Ankily
Clinical and Experimental Dental Research.2024;[Epub] CrossRef
Effects of Growth Factors on the Differentiation of Dental Stem Cells: A Systematic Review and Meta-analysis (Part I)
Sayna Shamszadeh, Armin Shirvani, Hassan Torabzadeh, Saeed Asgary
Current Stem Cell Research & Therapy.2024; 19(4): 523. CrossRef
The Role of Growth Factor Delivery Systems on Cellular Activities of Dental Stem Cells: A Systematic Review (Part II)
Sayna Shamszadeh, Armin Shirvani, Saeed Asgary
Current Stem Cell Research & Therapy.2024; 19(4): 587. CrossRef
Comprehensive review of composition, properties, clinical applications, and future perspectives of calcium-enriched mixture (CEM) cement: a systematic analysis
Saeed Asgary, Mahtab Aram, Mahta Fazlyab
BioMedical Engineering OnLine.2024;[Epub] CrossRef
Evaluation of dental pulp stem cells behavior after odontogenic differentiation induction by three different bioactive materials on two different scaffolds
Basma Ahmed, Mai H. Ragab, Rania A. Galhom, Hayam Y. Hassan
BMC Oral Health.2023;[Epub] CrossRef
Characterization of Dental Pulp Stem Cell Responses to Functional Biomaterials Including Mineralized Trioxide Aggregates
Sejin Bae, Bueonguk Kang, Hyungbin Lee, Harrison Luu, Eric Mullins, Karl Kingsley
Journal of Functional Biomaterials.2021; 12(1): 15. CrossRef
Incorporation of amoxicillin-loaded microspheres in mineral trioxide aggregate cement: an in vitro study
Fábio Rocha Bohns, Vicente Castelo Branco Leitune, Isadora Martini Garcia, Bruna Genari, Nélio Bairros Dornelles, Silvia Stanisçuaski Guterres, Fabrício Aulo Ogliari, Mary Anne Sampaio de Melo, Fabrício Mezzomo Collares
Restorative Dentistry & Endodontics.2020;[Epub] CrossRef

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Effects of the exposure site on histological pulpal responses after direct capping with 2 calcium-silicate based cements in a rat model: Panruethai Trongkij, Supachai Sutimuntanakul, Puangwan Lapthanasupkul, Chitpol Chaimanakarn, Rebecca Wong, Danuchit Banomyong; Restor Dent Endod 2018;43(4):e36. Published online August 22, 2018; DOI: https://doi.org/10.5395/rde.2018.43.e36

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Objectives

Direct pulp capping is a treatment for mechanically exposed pulp in which a biocompatible capping material is used to preserve pulpal vitality. Biocompatibility tests in animal studies have used a variety of experimental protocols, particularly with regard to the exposure site. In this study, pulp exposure on the occlusal and mesial surfaces of molar teeth was investigated in a rat model.

Materials and Methods

A total of 58 maxillary first molars of Wistar rats were used. Forty molars were mechanically exposed and randomly assigned according to 3 factors: 1) the exposure site (occlusal or mesial), 2) the pulp-capping material (ProRoot White MTA or Bio-MA), and 3) 2 follow-up periods (1 day or 7 days) (n = 5 each). The pulp of 6 intact molars served as negative controls. The pulp of 12 molars was exposed without a capping material (n = 3 per exposure site for each period) and served as positive controls. Inflammatory cell infiltration and reparative dentin formation were histologically evaluated at 1 and 7 days using grading scores.

Results

At 1 day, localized mild inflammation was detected in most teeth in all experimental groups. At 7 days, continuous/discontinuous calcified bridges were formed at exposure sites with no or few inflammatory cells. No significant differences in pulpal response according to the exposure site or calcium-silicate cement were observed.

Conclusions

The location of the exposure site had no effect on rat pulpal healing. However, mesial exposures could be performed easily, with more consistent results. The pulpal responses were not significantly different between the 2 capping materials.

Citations

Citations to this article as recorded by

The road map to proper dental pulp experiments in animal models
Nuha A Elmubarak
International Dental Journal of Student's Research.2024; 11(4): 163. CrossRef
Treatment outcomes of root perforations repaired by calcium silicate-based cements with or without an accelerator: A randomized controlled trial
Kanyarat Tungputsa, Danuchit Banomyong, Sittichoke Osiri, Supachai Sutimuntanakul
Endodontology.2024; 36(4): 315. CrossRef
Biological evaluation of novel phosphorylated pullulan‐based calcium hydroxide formulations as direct pulp capping materials: An in vivo study on a rat model
Md Refat Readul Islam, Rafiqul Islam, Yunqing Liu, Yu Toida, Yasuhiro Yoshida, Hidehiko Sano, Hany Mohamed Aly Ahmed, Atsushi Tomokiyo
International Endodontic Journal.2024; 57(9): 1247. CrossRef
3D-printed microgels supplemented with dentin matrix molecules as a novel biomaterial for direct pulp capping
Diana Cunha, Nayara Souza, Manuela Moreira, Nara Rodrigues, Paulo Silva, Cristiane Franca, Sivaporn Horsophonphong, Ashley Sercia, Ramesh Subbiah, Anthony Tahayeri, Jack Ferracane, Pamela Yelick, Vicente Saboia, Luiz Bertassoni
Clinical Oral Investigations.2022; 27(3): 1215. CrossRef
Calcium silicate and calcium aluminate cements for dentistry reviewed
Carolyn Primus, James L. Gutmann, Franklin R. Tay, Anna B. Fuks
Journal of the American Ceramic Society.2022; 105(3): 1841. CrossRef
Pulpal response to mineral trioxide aggregate containing phosphorylated pullulan-based capping material
Yu TOIDA, Shimpei KAWANO, Rafiqul ISLAM, Fu JIALE, AFM A CHOWDHURY, Shuhei HOSHIKA, Yasushi SHIMADA, Junji TAGAMI, Masahiro YOSHIYAMA, Satoshi INOUE, Ricardo M. CARVALHO, Yasuhiro YOSHIDA, Hidehiko SANO
Dental Materials Journal.2022; 41(1): 126. CrossRef
The Effect of Calcium-Silicate Cements on Reparative Dentinogenesis Following Direct Pulp Capping on Animal Models
Mihai Andrei, Raluca Paula Vacaru, Anca Coricovac, Radu Ilinca, Andreea Cristiana Didilescu, Ioana Demetrescu
Molecules.2021; 26(9): 2725. CrossRef
Histological evaluation of a novel phosphorylated pullulan‐based pulp capping material: An in vivo study on rat molars
Rafiqul Islam, Yu Toida, Fei Chen, Toru Tanaka, Satoshi Inoue, Tetsuya Kitamura, Yasuhiro Yoshida, Abu Faem Mohammad Almas Chowdhury, Hany Mohamed Aly Ahmed, Hidehiko Sano
International Endodontic Journal.2021; 54(10): 1902. CrossRef
Effectiveness of Direct Pulp Capping Bioactive Materials in Dentin Regeneration: A Systematic Review
Ermin Nie, Jiali Yu, Rui Jiang, Xiangzhen Liu, Xiang Li, Rafiqul Islam, Mohammad Khursheed Alam
Materials.2021; 14(22): 6811. CrossRef
A strontium and amorphous calcium phosphate dipped premixed injectable calcium silicate-based ceramic for dental root canal sealing
Huimin Jin, Yuzhu Li, Qingqing Wang, Menglu Dong, Mengmeng Yang, Wendy Chen, Shengrui Wang, Heng Zhang, Shunli Zheng, Chris Ying Cao, Zheng Zhou, Quan-Li Li
Ceramics International.2021; 47(23): 33738. CrossRef
Bioactive tri/dicalcium silicate cements for treatment of pulpal and periapical tissues
Carolyn M. Primus, Franklin R. Tay, Li-na Niu
Acta Biomaterialia.2019; 96: 35. CrossRef

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Basic Research

Gene expression profiling in human dental pulp cells treated with mineral trioxide aggregate: Yong-Beom Kim, Won-Jun Shon, WooCheol Lee, Kee-Yeon Kum, Seung-Ho Baek, Kwang-Shik Bae; J Korean Acad Conserv Dent 2010;35(3):152-163. Published online May 31, 2010; DOI: https://doi.org/10.5395/JKACD.2010.35.3.152

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This study investigated the changes in gene expression when mineral trioxide aggregate (MTA) was applied in vitro to human dental pulp cells (HDPCs). MTA in a teflon tube (diameter 10 mm, height 2 mm) was applied to HDPCs. Empty tube-applied HDPCs were used as negative control. For microarray analysis, total RNA was extracted at 6, 24, and 72 hrs after MTA application. The results were confirmed selectively by performing reverse transcriptase polymerase chain reaction for genes that showed changes of more than two-fold or less than half. Of the 24,546 genes, 109 genes were up-regulated greater than two-fold (e.g., FOSB, THBS1, BHLHB2, EDN1, IL11, FN1, COL10A1, and TUFT1) and 69 genes were down-regulated below 50% (e.g., SMAD6 and DCN). These results suggest that MTA, rather than being a bio-inert material, may have potential to affect the proliferation and differentiation of pulp cells in various ways.

Citations

Citations to this article as recorded by

Analysis of gene expression during odontogenic differentiation of cultured human dental pulp cells
Min-Seock Seo, Kyung-Gyun Hwang, Hyongbum Kim, Seung-Ho Baek
Restorative Dentistry & Endodontics.2012; 37(3): 142. CrossRef
Comparison of gene expression profiles of human dental pulp cells treated with mineral trioxide aggregate and calcium hydroxide
Yong-Beom Kim, Won-Jun Shon, Woocheol Lee, Kee-Yeon Kum, Seung-Ho Baek, Kwang-Shik Bae
Journal of Korean Academy of Conservative Dentistry.2011; 36(5): 397. CrossRef

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