Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Stem Cell Res Ther. 2014 Feb 28;5(1):31. [Epub ahead of print]

A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells.



During normal pulp tissue healing, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or interleukins, act in the initial 48 h (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 and/or reparative dentin formation. 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-alpha on the stem cell phenotype and differentiation ability of human DPCs.


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-alpha for 2 days and passaged to eliminate TNF-alpha completely. Analysis of stem cell phenotype was performed by quantification of cells positive for mesenchymal stem cell markers SSEA4 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.


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-alpha increased by two-fold 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-alpha treatment. A short-term TNF-alpha treatment also enhanced DPC function, including the ability to form cell colonies, to migrate and to differentiate into odontogenic and adipogenic lineages.


A short-term treatment with TNF-alpha enhanced the stem cell phenotype, migration and differentiation ability of DPCs.

[PubMed - as supplied by publisher]
Free PMC Article

Images from this publication.See all images (6)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk