Mesenchymal stem cells as active prohealing and immunosuppressive agents in periapical environment: evidence from human and experimental periapical lesions.

Abstract

INTRODUCTION:

Previous studies describe contrasting molecular profiles of active and inactive periapical granulomas characterized by distinct expression of cytokines, osteoclastogenic factors, and wound healing markers. Although the molecular mechanisms underlying such a dichotomy remain unknown, in this study we investigated the potential involvement of mesenchymal stem cells (MSCs) in determining human and murine periapical lesion activity and outcomes.

METHODS:

Periapical granulomas (n = 83) and control samples (n = 24) were comparatively assessed for the expression levels of 11 mesenchymal stem cell (MSC) markers using real-time polymerase chain reaction. Experimental periapical lesions induced in mice were evaluated for MSC marker expression and the effects of AMD3100 treatment on lesion outcomes.

RESULTS:

MCS marker expression was prevalent in periapical granulomas compared with that in controls, whereas CD29, CD73, CD90, CD146, CD166, NANOG, Stro-1, and CXCR4 expressions were higher in inactive than in active lesions. Experimental periapical lesion inactivity was also associated with an increased expression of MSC markers. The inhibition of MSC mobilization to the periapex by AMD3100 resulted in increased lesion sizes; decreased expression of MSCs and wound healing markers; and increased expression of interleukin 1 beta (IL-17β), interleukin 17 (IL-17), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and nuclear factor kappa-B ligand (RANKL).

CONCLUSIONS:

Our results show that MSC markers are overexpressed in inactive human and experimental periapical lesions and that MSC mobilization results in the attenuation of experimental lesion progression associated with immunosuppressive and prohealing mechanisms.

• Authors: Ana Claudia Araujo-Pires, Claudia Cristina Biguetti, Carlos Eduardo Repeke, Camila de Oliveira Rodini, Ana Paula Campanelli, Ana Paula Favaro Trombone, Ariadne Letra, Renato Menezes Silva, Gustavo Pompermaier Garlet
• Journal: Journal of endodontics (J Endod) Vol. 40 Issue 10 Pg. 1560-5 (Oct 2014) ISSN: 1878-3554 [Electronic] United States
• PMID: 25260726 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Chemical References

• Activated-Leukocyte Cell Adhesion Molecule
• Antigens, Surface
• Benzylamines
• Biomarkers
• CD146 Antigen
• Cyclams
• Heterocyclic Compounds
• Homeodomain Proteins
• Immunosuppressive Agents
• Integrin beta1
• Interleukin-17
• Interleukin-1beta
• RANK Ligand
• Receptors, CXCR4
• Thy-1 Antigens
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• 5'-Nucleotidase
• plerixafor

Topics

• 5'-Nucleotidase (analysis)
• Activated-Leukocyte Cell Adhesion Molecule (analysis)
• Adult
• Animals
• Antigens, Surface (analysis)
• Benzylamines
• Biomarkers (analysis)
• CD146 Antigen (analysis)
• Cyclams
• Disease Models, Animal
• Heterocyclic Compounds (therapeutic use)
• Homeodomain Proteins (analysis)
• Humans
• Immunosuppressive Agents (pharmacology)
• Integrin beta1 (analysis)
• Interferon-gamma (analysis)
• Interleukin-17 (analysis)
• Interleukin-1beta (analysis)
• Mesenchymal Stem Cells (drug effects, physiology)
• Mice
• Middle Aged
• Periapical Granuloma (drug therapy, pathology, physiopathology)
• Periapical Tissue (cytology, drug effects, physiology)
• RANK Ligand (analysis)
• Receptors, CXCR4 (analysis, antagonists & inhibitors)
• Thy-1 Antigens (analysis)
• Tumor Necrosis Factor-alpha (analysis)
• Wound Healing (physiology)