{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:48:39Z","timestamp":1790167719830,"version":"4.1.0"},"reference-count":162,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T00:00:00Z","timestamp":1685232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada (Discovery grant)","award":["AK-RGPIN-2020-05844"],"award-info":[{"award-number":["AK-RGPIN-2020-05844"]}]},{"name":"Dr. Lloyd and Mrs. Kay Chapman Chairship","award":["AK-RGPIN-2020-05844"],"award-info":[{"award-number":["AK-RGPIN-2020-05844"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Apical periodontitis is the inflammation and destruction of periradicular tissues, mediated by microbial factors originating from the infected pulp space. This bacteria-mediated inflammatory disease is known to interfere with root development in immature permanent teeth. Current research on interventions in immature teeth has been dedicated to facilitating the continuation of root development as well as regenerating the dentin\u2013pulp complex, but the fundamental knowledge on the cellular interactions and the role of periapical mediators in apical periodontitis in immature roots that govern the disease process and post-treatment healing is limited. The limitations in 2D monolayer cell culture have a substantial role in the existing limitations of understanding cell-to-cell interactions in the pulpal and periapical tissues. Three-dimensional (3D) tissue constructs with two or more different cell populations are a better physiological representation of in vivo environment. These systems allow the high-throughput testing of multi-cell interactions and can be applied to study the interactions between stem cells and immune cells, including the role of mediators\/cytokines in simulated environments. Well-designed 3D models are critical for understanding cellular functions and interactions in disease and healing processes for future therapeutic optimization in regenerative endodontics. This narrative review covers the fundamentals of (1) the disease process of apical periodontitis; (2) the influence and challenges of regeneration in immature roots; (3) the introduction of and crosstalk between mesenchymal stem cells and macrophages; (4) 3D cell culture techniques and their applications for studying cellular interactions in the pulpal and periapical tissues; (5) current investigations on cellular interactions in regenerative endodontics; and, lastly, (6) the dental\u2013pulp organoid developed for regenerative endodontics.<\/jats:p>","DOI":"10.3390\/biom13060900","type":"journal-article","created":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T15:30:47Z","timestamp":1685287847000},"page":"900","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["3D Organoids for Regenerative Endodontics"],"prefix":"10.3390","volume":"13","author":[{"given":"Fang-Chi","family":"Li","sequence":"first","affiliation":[{"name":"Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kishen","sequence":"additional","affiliation":[{"name":"Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/0030-4220(65)90166-0","article-title":"The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats","volume":"20","author":"Kakehashi","year":"1965","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1177\/154411130401500604","article-title":"Pathogenesis of Apical Periodontitis and the Causes of Endodontic Failures","volume":"15","author":"Nair","year":"2004","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1034\/j.1399-302x.2000.150301.x","article-title":"Protective and destructive immune reactions in apical periodontitis","volume":"15","author":"Kiss","year":"2000","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cden.2009.12.006","article-title":"Treatment of the Immature Tooth with a Non\u2013Vital Pulp and Apical Periodontitis","volume":"54","author":"Trope","year":"2010","journal-title":"Dent. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.joen.2019.05.008","article-title":"Comparison of the Effects of Intraradicular Materials on the Incidence of Fatal Root Fracture in Immature Teeth Treated with Mineral Trioxide Aggregate Apexification: A Retrospective Study","volume":"45","author":"Danwittayakorn","year":"2019","journal-title":"J. Endod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S95","DOI":"10.1016\/j.joen.2017.07.012","article-title":"Microbial Modulation of Stem Cells and Future Directions in Regenerative Endodontics","volume":"43","author":"Diogenes","year":"2017","journal-title":"J. Endod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.adaj.2016.01.009","article-title":"Regenerative endodontics: A way forward","volume":"147","author":"Diogenes","year":"2016","journal-title":"J. Am. Dent. Assoc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0099-2399(81)80125-2","article-title":"Quantitative analysis of cellular composition of human periapical granuloma","volume":"7","author":"Stern","year":"1981","journal-title":"J. Endod."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S0099-2399(07)80157-9","article-title":"Immune cells in periapical granuloma: Morphological and immunohistochemical characterization","volume":"17","author":"Piattelli","year":"1991","journal-title":"J. Endod."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1046\/j.1365-2591.2003.00627.x","article-title":"Inflammatory infiltrate of chronic periradicular lesions: An immunohistochemical study","volume":"36","author":"Liapatas","year":"2003","journal-title":"Int. Endod. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1034\/j.1600-9657.2000.016001001.x","article-title":"Macrophages in periapical lesions","volume":"16","author":"Metzger","year":"2000","journal-title":"Endod. Dent. Traumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jdsr.2018.03.001","article-title":"The roles of odontoblasts in dental pulp innate immunity","volume":"54","author":"Yumoto","year":"2018","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1128\/mr.60.2.316-341.1996","article-title":"Bacterial modulins: A novel class of virulence factors which cause host tissue pathology by inducing cytokine synthesis","volume":"60","author":"Henderson","year":"1996","journal-title":"Microbiol Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.joen.2015.01.017","article-title":"Proinflammatory Activity of Primarily Infected Endodontic Content against Macrophages after Different Phases of the Root Canal Therapy","volume":"41","author":"Marinho","year":"2015","journal-title":"J. Endod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1177\/10454411980090040701","article-title":"Periapical Inflammatory Responses and Their Modulation","volume":"9","author":"Stashenko","year":"1998","journal-title":"Crit. Rev. Oral Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/j.1600-9657.1994.tb00536.x","article-title":"Immunohistochemical examination on the localization of macrophages and plasma cells in induced rat periapical lesions","volume":"10","author":"Akamine","year":"1994","journal-title":"Endod. Dent. Traumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0099-2399(96)80266-4","article-title":"Kinetics of macrophages and lymphoid cells during the development of experimentally induced periapical lesions in rat molars: A quantitative immunohistochemical study","volume":"22","author":"Kawashima","year":"1996","journal-title":"J. Endod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1210\/endo.136.6.7750500","article-title":"Monocyte chemoattractant protein-1 expression and monocyte recruitment in osseous inflammation in the mouse","volume":"136","author":"Rahimi","year":"1995","journal-title":"Endocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1399-302X.1995.tb00145.x","article-title":"Immunolocalization of bone-resorptive cytokines in rat pulp and periapical lesions following surgical pulp exposure","volume":"10","author":"Wang","year":"1995","journal-title":"Oral Microbiol. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.4049\/jimmunol.138.5.1464","article-title":"Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption","volume":"138","author":"Stashenko","year":"1987","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0003-9969(90)90186-E","article-title":"Effects of cytokines on prostaglandin E and cAMP levels in human periodontal ligament fibroblasts in vitro","volume":"35","author":"Saito","year":"1990","journal-title":"Arch. Oral Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1600-0765.1989.tb02007.x","article-title":"Gingival fibroblasts degrade type I collagen films when stimulated with tumor necrosis factor and interleukin 1: Evidence that breakdown is mediated by metalloproteinases","volume":"24","author":"Meikle","year":"1898","journal-title":"J. Periodontal Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1159\/000235340","article-title":"Regulation of Immune Responses by T Cells with Different Cytokine Secretion Phenotypes: Role of a New Cytokine, Cytokine Synthesis Inhibitory Factor (IL10)","volume":"94","author":"Mosmann","year":"1991","journal-title":"Int. Arch. Allergy Appl. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.4049\/jimmunol.137.11.3544","article-title":"Recombinant human interferon-gamma inhibits formation of human osteoclast-like cells","volume":"137","author":"Takahashi","year":"1986","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/0006-291X(90)91550-C","article-title":"Interleukin-4 as a potent inhibitor of bone resorption","volume":"172","author":"Watanabe","year":"1990","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","first-page":"81","article-title":"Transforming growth factor-beta","volume":"12","author":"Cheifetz","year":"1992","journal-title":"Cancer Surv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1084\/jem.180.5.1587","article-title":"Transforming growth factor beta: The good, the bad, and the ugly","volume":"180","author":"Wahl","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0008-8749(90)90299-7","article-title":"Regulation of interleukin-2 and interleukin-6 production from T-cells: Involvement of interleukin-1 beta and transforming growth factor-beta","volume":"126","author":"Espevik","year":"1990","journal-title":"Cell Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41413-017-0005-4","article-title":"Transforming growth factor-\u03b2 in stem cells and tissue homeostasis","volume":"6","author":"Xu","year":"2018","journal-title":"Bone Res."},{"key":"ref_30","unstructured":"Hargreaves, K.M., and Goodis, H.E. (2002). Seltzer and Bender\u2019s Dental Pulp, Quintessence Publishing Co. Inc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.joen.2008.03.001","article-title":"The Hidden Treasure in Apical Papilla: The Potential Role in Pulp\/Dentin Regeneration and BioRoot Engineering","volume":"34","author":"Huang","year":"2008","journal-title":"J. Endod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1600-9657.1992.tb00228.x","article-title":"Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha. A retrospective clinical study","volume":"8","author":"Cvek","year":"1992","journal-title":"Endod. Dent. Traumatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.joen.2017.09.018","article-title":"The Effect of Long-term Dressing with Calcium Hydroxide on the Fracture Susceptibility of Teeth","volume":"44","author":"Kahler","year":"2018","journal-title":"J. Endod."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.jdent.2016.10.005","article-title":"Pulp and apical tissue response to deep caries in immature teeth: A histologic and histobacteriologic study","volume":"56","author":"Ricucci","year":"2017","journal-title":"J. Dent."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/ageing\/26.suppl_4.15","article-title":"Ageing, Defence Mechanisms and the Immune System","volume":"26","author":"Horan","year":"1997","journal-title":"Age Ageing"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.joen.2016.08.004","article-title":"Regenerative Characteristics of Apical Papilla\u2013derived Cells from Immature Teeth with Pulpal and Periapical Pathosis","volume":"42","author":"Yoo","year":"2016","journal-title":"J. Endod."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.joen.2016.09.024","article-title":"Survival of the Apical Papilla and Its Resident Stem Cells in a Case of Advanced Pulpal Necrosis and Apical Periodontitis","volume":"43","author":"Chrepa","year":"2017","journal-title":"J. Endod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S51","DOI":"10.1016\/j.joen.2008.02.032","article-title":"Regeneration potential of the young permanent tooth: What does the future hold?","volume":"34","author":"Hargreaves","year":"2008","journal-title":"J. Endod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.joen.2006.09.013","article-title":"Regenerative Endodontics: A Review of Current Status and a Call for Action","volume":"33","author":"Murray","year":"2007","journal-title":"J. Endod."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/etp.12040","article-title":"An update on clinical regenerative endodontics","volume":"28","author":"Diogenes","year":"2013","journal-title":"Endod. Top."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.joen.2013.10.027","article-title":"Regenerative Potential of Immature Permanent Teeth with Necrotic Pulps after Different Regenerative Protocols","volume":"40","author":"Nagy","year":"2014","journal-title":"J. Endod."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.joen.2013.10.032","article-title":"Revascularization Outcomes: A Prospective Analysis of 16 Consecutive Cases","volume":"40","author":"Kahler","year":"2014","journal-title":"J. Endod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/j.joen.2017.06.023","article-title":"Regenerative Endodontics Versus Apexification in Immature Permanent Teeth with Apical Periodontitis: A Prospective Randomized Controlled Study","volume":"43","author":"Lin","year":"2017","journal-title":"J. Endod."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.joen.2019.02.002","article-title":"Evaluation of Blood Clot, Platelet-rich Plasma, Platelet-rich Fibrin, and Platelet Pellet as Scaffolds in Regenerative Endodontic Treatment: A Prospective Randomized Trial","volume":"45","author":"Ulusoy","year":"2019","journal-title":"J. Endod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.joen.2013.04.032","article-title":"Clinical, Radiographic, and Histological Observation of a Human Immature Permanent Tooth with Chronic Apical Abscess after Revitalization Treatment","volume":"39","author":"Shimizu","year":"2013","journal-title":"J. Endod."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.joen.2012.09.015","article-title":"Histological Findings of Revascularized\/Revitalized Immature Permanent Molar with Apical Periodontitis Using Platelet-rich Plasma","volume":"39","author":"Martin","year":"2013","journal-title":"J. Endod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1089\/ten.tec.2017.0342","article-title":"A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue","volume":"24","author":"Zhu","year":"2018","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1177\/0022034520913242","article-title":"Cell-Based Regenerative Endodontics for Treatment of Periapical Lesions: A Randomized, Controlled Phase I\/II Clinical Trial","volume":"99","author":"Brizuela","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1089\/ten.tea.2010.0181","article-title":"Regeneration of Dental-Pulp-like Tissue by Chemotaxis-Induced Cell Homing","volume":"16","author":"Kim","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.biomaterials.2014.12.006","article-title":"Autophagy in SDF-1\u03b1-mediated DPSC migration and pulp regeneration","volume":"44","author":"Yang","year":"2015","journal-title":"Biomaterials"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1002\/jor.1100090504","article-title":"Mesenchymal stem cells","volume":"9","author":"Caplan","year":"1991","journal-title":"J. Orthop. Res."},{"key":"ref_52","first-page":"215","article-title":"Mesenchymal stem cells: Characteristics and clinical applications","volume":"44","author":"Bobis","year":"2006","journal-title":"Folia Histochem. et Cytobiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0094-1298(20)31020-8","article-title":"The Mesengenic Process","volume":"21","author":"Caplan","year":"1994","journal-title":"Clin. Plast. Surg."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jpor.2012.06.001","article-title":"Stem cells in dentistry--part I: Stem cell sources","volume":"56","author":"Egusa","year":"2012","journal-title":"J. Prosthodont. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.joen.2007.11.021","article-title":"Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: A pilot study","volume":"34","author":"Sonoyama","year":"2008","journal-title":"J. Endod."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e79","DOI":"10.1371\/journal.pone.0000079","article-title":"Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine","volume":"1","author":"Sonoyama","year":"2006","journal-title":"PLoS ONE"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1600-0765.1999.tb02217.x","article-title":"Evidence that laminin-5 is a component of the tooth surface internal basal lamina, supporting epithelial cell adhesion","volume":"34","author":"Mullen","year":"1999","journal-title":"J. Periodontal Res."},{"key":"ref_58","first-page":"405","article-title":"Comparative analysis of TGF beta s, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation","volume":"38","author":"Smith","year":"1994","journal-title":"Int. J. Dev. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1016\/j.archoralbio.2013.06.018","article-title":"Comparative characterization of STRO-1(neg)\/CD146(pos) and STRO-1(pos)\/CD146(pos) apical papilla stem cells enriched with flow cytometry","volume":"58","author":"Bakopoulou","year":"2013","journal-title":"Arch. Oral Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.yexcr.2013.10.005","article-title":"Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor","volume":"320","author":"Patil","year":"2014","journal-title":"Exp. Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6104738","DOI":"10.1155\/2019\/6104738","article-title":"Stem Cells from the Apical Papilla: A Promising Source for Stem Cell-Based Therapy","volume":"2019","author":"Kang","year":"2019","journal-title":"BioMed Res. Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.joen.2017.01.023","article-title":"Effect of Bacterial Biofilm on the Osteogenic Differentiation of Stem Cells of Apical Papilla","volume":"43","author":"Vishwanat","year":"2017","journal-title":"J. Endod."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.joen.2020.01.009","article-title":"Lipopolysaccharide Downregulates the Osteo-\/Odontogenic Differentiation of Stem Cells from Apical Papilla by Inducing Autophagy","volume":"46","author":"Lei","year":"2020","journal-title":"J. Endod."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1111\/iej.12551","article-title":"Long-term exposure to pro-inflammatory cytokines inhibits the osteogenic\/dentinogenic differentiation of stem cells from the apical papilla","volume":"49","author":"Liu","year":"2016","journal-title":"Int. Endod. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1002\/eji.200737638","article-title":"The macrophage: Past, present and future","volume":"37","author":"Gordon","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1067\/moe.2001.116813","article-title":"Study of the expression of CD68+ macrophages and CD8+ T cells in human granulomas and periapical cysts","volume":"92","author":"Rodini","year":"2001","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endodontol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.it.2004.09.015","article-title":"The chemokine system in diverse forms of macrophage activation and polarization","volume":"25","author":"Mantovani","year":"2004","journal-title":"Trends Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/path.4133","article-title":"Macrophage plasticity and polarization in tissue repair and remodelling","volume":"229","author":"Mantovani","year":"2013","journal-title":"J. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"614","DOI":"10.3389\/fimmu.2014.00614","article-title":"Molecular mechanisms that influence the macrophage m1-m2 polarization balance","volume":"5","author":"Wang","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"792","DOI":"10.3389\/fimmu.2019.00792","article-title":"Macrophage Polarization in Physiological and Pathological Pregnancy","volume":"10","author":"Yao","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"20180089","DOI":"10.1098\/rsfs.2018.0089","article-title":"Mesenchymal stem cell-based bioengineered constructs: Foreign body response, cross-talk with macrophages and impact of biomaterial design strategies for pelvic floor disorders","volume":"9","author":"Mukherjee","year":"2019","journal-title":"Interface Focus"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.semnephrol.2010.03.002","article-title":"Monocyte and Macrophage Biology: An Overview","volume":"30","author":"Rees","year":"2010","journal-title":"Semin. Nephrol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.bbmt.2017.04.006","article-title":"Commentary: Role of Mesenchymal Stromal Cell\u2013Mediated Crosstalk with Macrophages in Graft-versus-Host Disease and Tissue Repair","volume":"23","author":"Davies","year":"2017","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.4049\/jimmunol.177.10.7303","article-title":"Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression","volume":"177","author":"Martinez","year":"2006","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/ni.1937","article-title":"Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm","volume":"11","author":"Biswas","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"453","DOI":"10.2741\/2692","article-title":"Macrophage activation and polarization","volume":"13","author":"Martinez","year":"2008","journal-title":"Front. Biosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4571","DOI":"10.1007\/s00784-020-03324-2","article-title":"Macrophages skew towards M1 profile through reduced CD163 expression in symptomatic apical periodontitis","volume":"24","author":"Veloso","year":"2020","journal-title":"Clin. Oral Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00784-017-2123-1","article-title":"Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts","volume":"22","author":"Weber","year":"2018","journal-title":"Clin. Oral Investig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.joen.2022.01.003","article-title":"Local Immunomodulatory Effects of Intracanal Medications in Apical Periodontitis","volume":"48","author":"Hussein","year":"2022","journal-title":"J. Endod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.dental.2023.03.013","article-title":"Next-generation biomaterials for dental pulp tissue immunomodulation","volume":"39","author":"Swanson","year":"2023","journal-title":"Dent. Mater."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.biomaterials.2017.12.025","article-title":"Mesenchymal stem cell-macrophage crosstalk and bone healing","volume":"196","author":"Pajarinen","year":"2019","journal-title":"Biomaterials"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"681171","DOI":"10.3389\/fcell.2021.681171","article-title":"Mesenchymal Stem Cell-Macrophage Crosstalk and Maintenance of Inflammatory Microenvironment Homeostasis","volume":"9","author":"Lu","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/jcb.25394","article-title":"Macrophage-Associated Osteoactivin\/GPNMB Mediates Mesenchymal Stem Cell Survival, Proliferation, and Migration Via a CD44-Dependent Mechanism","volume":"117","author":"Yu","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e8970","DOI":"10.7717\/peerj.8970","article-title":"Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells","volume":"8","author":"Xia","year":"2020","journal-title":"PeerJ"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.stem.2008.03.003","article-title":"Efficient Homing of Multipotent Adult Mesenchymal Stem Cells Depends on FROUNT-Mediated Clustering of CCR2","volume":"2","author":"Uchida","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1002\/art.24330","article-title":"Stromal cell-derived factor 1\/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model","volume":"60","author":"Kitaori","year":"2009","journal-title":"Arthritis. Rheum."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/stem.1040","article-title":"Induction of osteogenesis in mesenchymal stem cells by activated monocytes\/macrophages depends on oncostatin M signaling","volume":"30","author":"Guihard","year":"2012","journal-title":"Stem Cells"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1302\/2046-3758.810.BJR-2018-0231.R2","article-title":"Precise immunomodulation of the M1 to M2 macrophage transition enhances mesenchymal stem cell osteogenesis and differs by sex","volume":"8","author":"Nathan","year":"2019","journal-title":"Bone Jt. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/term.2826","article-title":"Coculture with monocytes\/macrophages modulates osteogenic differentiation of adipose-derived mesenchymal stromal cells on poly(lactic-co-glycolic) acid\/polycaprolactone scaffolds","volume":"13","author":"Tang","year":"2019","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nm.1905","article-title":"Bone marrow stromal cells attenuate sepsis via prostaglandin E2\u2013dependent reprogramming of host macrophages to increase their interleukin-10 production","volume":"15","author":"Leelahavanichkul","year":"2009","journal-title":"Nat. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1038\/mt.2015.131","article-title":"Suppression of IL-7-dependent Effector T-cell Expansion by Multipotent Adult Progenitor Cells and PGE2","volume":"23","author":"Reading","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_93","first-page":"394917","article-title":"Immunoregulation by Mesenchymal Stem Cells: Biological Aspects and Clinical Applications","volume":"2015","author":"Montesinos","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.stem.2007.11.014","article-title":"Mesenchymal Stem Cell-Mediated Immunosuppression Occurs via Concerted Action of Chemokines and Nitric Oxide","volume":"2","author":"Ren","year":"2008","journal-title":"Cell Stem Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41423-019-0204-6","article-title":"Cell\u2013cell contact with proinflammatory macrophages enhances the immunotherapeutic effect of mesenchymal stem cells in two abortion models","volume":"16","author":"Li","year":"2019","journal-title":"Cell. Mol. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Maggini, J., Mirkin, G., Geffner, J.R., Bognanni, I., Holmberg, J., Piazz\u00f3n, I.M., Nepomnaschy, I., Costa, H., Ca\u00f1ones, C., and Raiden, S. (2010). Mouse Bone Marrow-Derived Mesenchymal Stromal Cells Turn Activated Macrophages into a Regulatory-Like Profile. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009252"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2047-1440-1-12","article-title":"Mesenchymal stem cell-educated macrophages","volume":"1","author":"Eggenhofer","year":"2012","journal-title":"Transplant. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"552","DOI":"10.4252\/wjsc.v6.i5.552","article-title":"Secretion of immunoregulatory cytokines by mesenchymal stem cells","volume":"6","author":"Kyurkchiev","year":"2014","journal-title":"World J. Stem Cells"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3389\/fimmu.2014.00148","article-title":"The Life and Fate of Mesenchymal Stem Cells","volume":"5","author":"Eggenhofer","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1186\/s13287-019-1447-y","article-title":"MSC-secreted TGF-\u03b2 regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt\/FoxO1 pathway","volume":"10","author":"Liu","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.tcb.2011.09.005","article-title":"From 3D cell culture to organs-on-chips","volume":"21","author":"Huh","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1083\/jcb.201610056","article-title":"Organoids: A historical perspective of thinking in three dimensions","volume":"216","author":"Simian","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/S1359-6446(02)02273-0","article-title":"Engineering cellular microenvironments to improve cell-based drug testing","volume":"7","author":"Bhadriraju","year":"2002","journal-title":"Drug Discov. Today"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1089\/adt.2014.573","article-title":"Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors","volume":"12","author":"Edmondson","year":"2014","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/teb.2007.0150","article-title":"Three-Dimensional Cell Culture Matrices: State of the Art","volume":"14","author":"Lee","year":"2008","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ygyno.2008.11.032","article-title":"Multicellular spheroids in ovarian cancer metastases: Biology and pathology","volume":"113","author":"Shield","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.4081\/ejh.2010.e46","article-title":"Human dental pulp stem cells produce mineralized matrix in 2D and 3D cultures","volume":"54","author":"Riccio","year":"2010","journal-title":"Eur. J. Histochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.archoralbio.2013.12.006","article-title":"Three-dimensional spheroid culture promotes odonto\/osteoblastic differentiation of dental pulp cells","volume":"59","author":"Yamamoto","year":"2014","journal-title":"Arch. Oral Biol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s13770-019-00203-0","article-title":"Three-Dimensional Spheroid Formation of Cryopreserved Human Dental Follicle-Derived Stem Cells Enhances Pluripotency and Osteogenic Induction Properties","volume":"16","author":"Kim","year":"2019","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.3389\/fphar.2019.01576","article-title":"Three-Dimensional Culture Promotes the Differentiation of Human Dental Pulp Mesenchymal Stem Cells into Insulin-Producing Cells for Improving the Diabetes Therapy","volume":"10","author":"Xu","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Bu, N.-U., Lee, H.-S., Lee, B.-N., Hwang, Y.-C., Kim, S.-Y., Chang, S.W., Choi, K.-K., Kim, D.-S., and Jang, J.-H. (2020). In Vitro Characterization of Dental Pulp Stem Cells Cultured in Two Microsphere-Forming Culture Plates. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010242"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/j.joen.2017.06.004","article-title":"Properties of Dental Pulp\u2013derived Mesenchymal Stem Cells and the Effects of Culture Conditions","volume":"43","author":"Kawashima","year":"2017","journal-title":"J. Endod."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Jeong, Y.Y., Kim, M.S., Lee, K.E., Nam, O.H., Jang, J.-H., Choi, S.-C., and Lee, H.-S. (2021). Comparison of 2- and 3-Dimensional Cultured Periodontal Ligament Stem Cells; a Pilot Study. Appl. Sci., 11.","DOI":"10.3390\/app11031083"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Banavar, S.R., Rawal, S.Y., Pulikkotil, S.J., Daood, U., Paterson, I.C., Davamani, F.A., Kajiya, M., Kurihara, H., SKhoo, P., and Tan, E.L. (2021). 3D Clumps\/Extracellular Matrix Complexes of Periodontal Ligament Stem Cells Ameliorate the Attenuating Effects of LPS on Proliferation and Osteogenic Potential. J. Pers. Med., 11.","DOI":"10.3390\/jpm11060528"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1177\/0022034518772260","article-title":"Pulp Regeneration by 3-dimensional Dental Pulp Stem Cell Constructs","volume":"97","author":"Itoh","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.archoralbio.2018.02.008","article-title":"A comprehensive analysis of human dental pulp cell spheroids in a three-dimensional pellet culture system","volume":"91","author":"Zhang","year":"2018","journal-title":"Arch. Oral Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1089\/ten.tec.2011.0367","article-title":"A Three-Dimensional Cell Culture Model to Study the Mechano-Biological Behavior in Periodontal Ligament Regeneration","volume":"18","author":"Oortgiesen","year":"2012","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.actbio.2019.05.024","article-title":"A rapid biofabrication technique for self-assembled collagen-based multicellular and heterogeneous 3D tissue constructs","volume":"92","author":"Selvaganapathy","year":"2019","journal-title":"Acta Biomater."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s00441-005-0148-2","article-title":"Dynamic analysis of hepatoma spheroid formation: Roles of E-cadherin and beta1-integrin","volume":"324","author":"Lin","year":"2006","journal-title":"Cell Tissue Res."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00253-014-6253-y","article-title":"Hydrogels for 3D mammalian cell culture: A starting guide for laboratory practice","volume":"99","author":"Ruedinger","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"McGuigan, A.P., Bruzewicz, D.A., Glavan, A., Butte, D.A., Butte, M., and Whitesides, G.M. (2008). Cell encapsulation in sub-mm sized gel modules using replica molding. PLoS ONE, 3.","DOI":"10.1371\/annotation\/0a0b70a9-a6e0-4e60-b6bd-8ef894ed22cd"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1152\/physiol.00036.2016","article-title":"Modeling Physiological Events in 2D vs. 3D Cell Culture","volume":"32","author":"Duval","year":"2017","journal-title":"Physiology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3389\/fmolb.2020.00033","article-title":"Is It Time to Start Transitioning from 2D to 3D Cell Culture?","volume":"7","author":"Jensen","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fphar.2018.00006","article-title":"Three-Dimensional","volume":"9","author":"Langhans","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1080\/10463356.2010.11883480","article-title":"Three-dimensional matrices for anti-cancer drug testing and development","volume":"25","author":"Gurski","year":"2010","journal-title":"Oncol. Issues"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"5517","DOI":"10.3390\/ijms16035517","article-title":"Three-Dimensional Cell Culture: A Breakthrough in Vivo","volume":"16","author":"Antoni","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1177\/2472555219830087","article-title":"3D Cell-Based Assays for Drug Screens: Challenges in Imaging, Image Analysis, and High-Content Analysis","volume":"24","author":"Booij","year":"2019","journal-title":"SLAS Discov."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.joen.2022.02.011","article-title":"Engineering a Novel Stem Cells from Apical Papilla-Macrophages Organoid for Regenerative Endodontics","volume":"48","author":"Li","year":"2022","journal-title":"J. Endod."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.joen.2022.04.011","article-title":"Deciphering Stem Cell from Apical Papilla\u2013Macrophage Choreography Using a Novel 3-dimensional Organoid System","volume":"48","author":"Li","year":"2022","journal-title":"J. Endod."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1590\/S0103-64402011000200001","article-title":"Mesenchymal stem cells in the dental tissues: Perspectives for tissue regeneration","volume":"22","author":"Estrela","year":"2011","journal-title":"Braz. Dent. J."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1016\/j.joen.2013.07.018","article-title":"Human Stem Cells from the Apical Papilla Response to Bacterial Lipopolysaccharide Exposure and Anti-inflammatory Effects of Nuclear Factor I C","volume":"39","author":"Zhang","year":"2013","journal-title":"J. Endod."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1016\/j.joen.2017.06.024","article-title":"Effects of Lipopolysaccharide on the Proliferation and Osteogenic Differentiation of Stem Cells from the Apical Papilla","volume":"43","author":"Lertchirakarn","year":"2017","journal-title":"J. Endod."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.joen.2021.03.010","article-title":"The Role of Small Extracellular Vesicles Derived from Lipopolysaccharide-preconditioned Human Dental Pulp Stem Cells in Dental Pulp Regeneration","volume":"47","author":"Chen","year":"2021","journal-title":"J. Endod."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"20140065","DOI":"10.1098\/rsif.2014.0065","article-title":"Co-culture systems and technologies: Taking synthetic biology to the next level","volume":"11","author":"Goers","year":"2014","journal-title":"J. R. Soc. Interface"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"911","DOI":"10.3389\/fbioe.2020.00911","article-title":"Impact of Culture Medium on Cellular Interactions in in vitro Co-culture Systems","volume":"8","author":"Vis","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/bit.22361","article-title":"Hydrogels as extracellular matrix mimics for 3D cell culture","volume":"103","author":"Tibbitt","year":"2009","journal-title":"Biotechnol. Bioeng."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Luca, A.C., Mersch, S., Deenen, R., Schmidt, S., Messner, I., Sch\u00e4fer, K.-L., Baldus, S.E., Huckenbeck, W., Piekorz, R.P., and Knoefel, W.T. (2013). Impact of the 3D Microenvironment on Phenotype, Gene Expression, and EGFR Inhibition of Colorectal Cancer Cell Lines. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059689"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Huang, H., Ding, Y., Sun, X.S., and Nguyen, T.A. (2013). Peptide Hydrogelation and Cell Encapsulation for 3D Culture of MCF-7 Breast Cancer Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059482"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/j.copbio.2013.04.011","article-title":"Extracellular matrix signaling in morphogenesis and repair","volume":"24","author":"Clause","year":"2013","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1124\/pr.109.001289","article-title":"Extracellular Matrix Molecules: Potential Targets in Pharmacotherapy","volume":"61","author":"Sainio","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"109487","DOI":"10.1016\/j.cellsig.2019.109487","article-title":"Extracellular matrix-cell interactions: Focus on therapeutic applications","volume":"66","author":"Sainio","year":"2020","journal-title":"Cell Signal."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/iej.13283","article-title":"Efficacy of bioactive nanoparticles on tissue-endotoxin induced suppression of stem cell viability, migration and differentiation","volume":"53","author":"Kukreti","year":"2020","journal-title":"Int. Endod. J."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1159\/000276589","article-title":"Suppression of T Cell Proliferation by Root Apical Papilla Stem Cells in vitro","volume":"191","author":"Ding","year":"2010","journal-title":"Cells Tissues Organs"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"3955","DOI":"10.1016\/j.transproceed.2011.08.102","article-title":"Swine Dental Pulp Stem Cells Inhibit T-Cell Proliferation","volume":"43","author":"Tang","year":"2011","journal-title":"Transplant. Proc."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.joen.2011.12.024","article-title":"Coculture of dental pulp stem cells with endothelial cells enhances osteo-\/odontogenic and angiogenic potential in vitro","volume":"38","author":"Dissanayaka","year":"2012","journal-title":"J. Endod."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1089\/ten.tea.2014.0058","article-title":"Coculture of stem cells from apical papilla and human umbilical vein endothelial cell under hypoxia increases the formation of three-dimensional vessel-like structures in vitro","volume":"21","author":"Yuan","year":"2015","journal-title":"Tissue Eng. Part A"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1016\/j.joen.2016.05.012","article-title":"EphrinB2 Stabilizes Vascularlike Structures Generated by Endothelial Cells and Stem Cells from Apical Papilla","volume":"42","author":"Yuan","year":"2016","journal-title":"J. Endod."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1177\/0022034516657817","article-title":"DPSCs from Inflamed Pulp Modulate Macrophage Function via the TNF-\u03b1\/IDO Axis","volume":"95","author":"Lee","year":"2016","journal-title":"J. Dent. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/jdi.12452","article-title":"Transplantation of dental pulp stem cells suppressed inflammation in sciatic nerves by promoting macrophage polarization towards anti-inflammation phenotypes and ameliorated diabetic polyneuropathy","volume":"7","author":"Omi","year":"2016","journal-title":"J. Diabetes Investig."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s13770-017-0061-2","article-title":"Co-culture of Human Dental Pulp Stem Cells and Endothelial Cells Using Porous Biopolymer Microcarriers: A Feasibility Study for Bone Tissue Engineering","volume":"14","author":"Jin","year":"2017","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1007\/s00018-018-2764-5","article-title":"Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion","volume":"75","author":"Bottemanne","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.joen.2018.03.018","article-title":"Characterization of the Cellular Responses of Dental Mesenchymal Stem Cells to the Immune System","volume":"44","author":"Whiting","year":"2018","journal-title":"J. Endod."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"14015","DOI":"10.1038\/s41598-019-50367-x","article-title":"Stem cells from the dental apical papilla in extracellular matrix hydrogels mitigate inflammation of microglial cells","volume":"9","author":"Tatic","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1111\/iej.13197","article-title":"Potential immunomodulatory effects of stem cells from the apical papilla on Treg conversion in tissue regeneration for regenerative endodontic treatment","volume":"52","author":"Liu","year":"2019","journal-title":"Int. Endod. J."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.1111\/jcmm.16071","article-title":"Dental pulp\u2013derived stem cells inhibit osteoclast differentiation by secreting osteoprotegerin and deactivating AKT signalling in myeloid cells","volume":"25","author":"Kanji","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"609204","DOI":"10.3389\/fcell.2020.609204","article-title":"Human Dental Pulp Stem Cells Modulate Cytokine Production in vitro by Peripheral Blood Mononuclear Cells from Coronavirus Disease 2019 Patients","volume":"8","author":"Croci","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Anderson, S., Prateeksha, P., and Das, H. (2022). Dental Pulp-Derived Stem Cells Reduce Inflammation, Accelerate Wound Healing and Mediate M2 Polarization of Myeloid Cells. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081999"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.joen.2022.09.001","article-title":"Neuroregenerative Potential of Stem-Cells-from-Apical-Papilla\u2013Derived Neuronal Cell Spheroids Regulated by Stem Cells from Apical Papillae Under Various Microenvironments in a Pulp-On-Chip System","volume":"48","author":"Luo","year":"2022","journal-title":"J. Endod."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Li, F.-C. (2021). Deciphering Stem Cell from Apical Papilla\u2014Macrophage Choreography in Inflammatory Environment Using a Novel 3D Organoid. [Ph.D. Thesis, University of Toronto].","DOI":"10.1016\/j.joen.2022.04.011"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1247125","DOI":"10.1126\/science.1247125","article-title":"Organogenesis in a dish: Modeling development and disease using organoid technologies","volume":"345","author":"Lancaster","year":"2014","journal-title":"Science"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Jeong, S.Y., Lee, S., Choi, W.H., Jee, J.H., Kim, H.-R., and Yoo, J. (2020). Fabrication of Dentin-Pulp-Like Organoids Using Dental-Pulp Stem Cells. Cells, 9.","DOI":"10.3390\/cells9030642"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/iej.13641","article-title":"Human three-dimensional dental pulp organoid model for toxicity screening of dental materials on dental pulp cells and tissue","volume":"55","author":"Xu","year":"2022","journal-title":"Int. Endod. J."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/6\/900\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:44:00Z","timestamp":1760125440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/6\/900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,28]]},"references-count":162,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["biom13060900"],"URL":"https:\/\/doi.org\/10.3390\/biom13060900","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,28]]}}}