Cargando…
A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells
INTRODUCTION: During normal pulp tissue healing, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) or interleukins, act in the initial 48 hours (inflammatory phase) and play important roles not only as chemo-attractants of inflammatory cells and stem/progenitor cells but also in in...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055131/ https://www.ncbi.nlm.nih.gov/pubmed/24580841 http://dx.doi.org/10.1186/scrt420 |
_version_ | 1782320605180198912 |
---|---|
author | Ueda, Mayu Fujisawa, Takuo Ono, Mitsuaki Hara, Emilio Satoshi Pham, Hai Thanh Nakajima, Ryu Sonoyama, Wataru Kuboki, Takuo |
author_facet | Ueda, Mayu Fujisawa, Takuo Ono, Mitsuaki Hara, Emilio Satoshi Pham, Hai Thanh Nakajima, Ryu Sonoyama, Wataru Kuboki, Takuo |
author_sort | Ueda, Mayu |
collection | PubMed |
description | INTRODUCTION: During normal pulp tissue healing, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) or interleukins, act in the initial 48 hours (inflammatory phase) and play important roles not only as chemo-attractants of inflammatory cells and stem/progenitor cells but also in inducing a cascade of reactions toward tissue regeneration or reparative dentin formation or both. Previous reports have shown that inflammatory cytokines regulate the differentiation capacity of dental pulp stem/progenitor cells (DPCs), but none has interrogated the impact of these cytokines on the stem cell phenotype of stem/progenitor cells. This study investigated the effects of a short-term treatment with TNF-α on the stem cell phenotype and differentiation ability of human DPCs. METHODS: An in vivo mouse model of pulp exposure was performed for analysis of expression of the mesenchymal stem cell marker CD146 in DPCs during the initial stage of inflammatory response. For in vitro studies, human DPCs were isolated and incubated with TNF-α for 2 days and passaged to eliminate TNF-α completely. Analysis of stem cell phenotype was performed by quantification of cells positive for mesenchymal stem cell markers SSEA-4 (stage-specific embryonic antigen 4) and CD146 by flow cytometry as well as by quantitative analysis of telomerase activity and mRNA levels of OCT-4 and NANOG. Cell migration, colony-forming ability, and differentiation toward odontogenesis and adipogenesis were also investigated. RESULTS: The pulp exposure model revealed a strong staining for CD146 during the initial inflammatory response, at 2 days after pulp exposure. In vitro experiments demonstrated that a short-term (2-day) treatment of TNF-α increased by twofold the percentage of SSEA-4(+) cells. Accordingly, STRO-1, CD146, and SSEA-4 protein levels as well as OCT-4 and NANOG mRNA levels were also significantly upregulated upon TNF-α treatment. A short-term TNF-α treatment also enhanced DPC function, including the ability to form cell colonies, to migrate, and to differentiate into odontogenic and adipogenic lineages. CONCLUSIONS: A short-term treatment with TNF-α enhanced the stem cell phenotype, migration, and differentiation ability of DPCs. |
format | Online Article Text |
id | pubmed-4055131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40551312014-06-15 A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells Ueda, Mayu Fujisawa, Takuo Ono, Mitsuaki Hara, Emilio Satoshi Pham, Hai Thanh Nakajima, Ryu Sonoyama, Wataru Kuboki, Takuo Stem Cell Res Ther Research INTRODUCTION: During normal pulp tissue healing, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) or interleukins, act in the initial 48 hours (inflammatory phase) and play important roles not only as chemo-attractants of inflammatory cells and stem/progenitor cells but also in inducing a cascade of reactions toward tissue regeneration or reparative dentin formation or both. Previous reports have shown that inflammatory cytokines regulate the differentiation capacity of dental pulp stem/progenitor cells (DPCs), but none has interrogated the impact of these cytokines on the stem cell phenotype of stem/progenitor cells. This study investigated the effects of a short-term treatment with TNF-α on the stem cell phenotype and differentiation ability of human DPCs. METHODS: An in vivo mouse model of pulp exposure was performed for analysis of expression of the mesenchymal stem cell marker CD146 in DPCs during the initial stage of inflammatory response. For in vitro studies, human DPCs were isolated and incubated with TNF-α for 2 days and passaged to eliminate TNF-α completely. Analysis of stem cell phenotype was performed by quantification of cells positive for mesenchymal stem cell markers SSEA-4 (stage-specific embryonic antigen 4) and CD146 by flow cytometry as well as by quantitative analysis of telomerase activity and mRNA levels of OCT-4 and NANOG. Cell migration, colony-forming ability, and differentiation toward odontogenesis and adipogenesis were also investigated. RESULTS: The pulp exposure model revealed a strong staining for CD146 during the initial inflammatory response, at 2 days after pulp exposure. In vitro experiments demonstrated that a short-term (2-day) treatment of TNF-α increased by twofold the percentage of SSEA-4(+) cells. Accordingly, STRO-1, CD146, and SSEA-4 protein levels as well as OCT-4 and NANOG mRNA levels were also significantly upregulated upon TNF-α treatment. A short-term TNF-α treatment also enhanced DPC function, including the ability to form cell colonies, to migrate, and to differentiate into odontogenic and adipogenic lineages. CONCLUSIONS: A short-term treatment with TNF-α enhanced the stem cell phenotype, migration, and differentiation ability of DPCs. BioMed Central 2014-02-28 /pmc/articles/PMC4055131/ /pubmed/24580841 http://dx.doi.org/10.1186/scrt420 Text en Copyright © 2014 Ueda et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Research Ueda, Mayu Fujisawa, Takuo Ono, Mitsuaki Hara, Emilio Satoshi Pham, Hai Thanh Nakajima, Ryu Sonoyama, Wataru Kuboki, Takuo A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells |
title | A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells |
title_full | A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells |
title_fullStr | A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells |
title_full_unstemmed | A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells |
title_short | A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells |
title_sort | short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055131/ https://www.ncbi.nlm.nih.gov/pubmed/24580841 http://dx.doi.org/10.1186/scrt420 |
work_keys_str_mv | AT uedamayu ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT fujisawatakuo ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT onomitsuaki ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT haraemiliosatoshi ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT phamhaithanh ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT nakajimaryu ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT sonoyamawataru ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT kubokitakuo ashorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT uedamayu shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT fujisawatakuo shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT onomitsuaki shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT haraemiliosatoshi shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT phamhaithanh shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT nakajimaryu shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT sonoyamawataru shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells AT kubokitakuo shorttermtreatmentwithtumornecrosisfactoralphaenhancesstemcellphenotypeofhumandentalpulpcells |