IADR Abstract Archives
The Immunomodulatory Properties of Dental Pulp Stem Cells
Objectives: Dental pulp is a cell rich connective tissue, where resident cells are programmed to perform specialised functions to maintain a homeostatic environment. Dental pulp contains several immunocompetent cells that orchestrate a protective response to injury or microbial invasion. Dental pulp stem cells (DPSCs) are specialized mesenchymal stem cells present in the dental pulp which are known to have high proliferative and differentiation capabilities. Recently, it has become apparent that these cells have multifunctional roles. Indeed, evidence suggests they also have intricate immunomodulatory properties.
Methods: A holistic approach to uncover the immunomodulatory properties of DPSCs was undertaken using NanostringTM technology. DPSCs were stimulated with Toll like receptor (TLR) ligands for 4 and 24 h and changes in levels of mRNA expression of 800 immunoregulatory molecules determined using the NanostringTM immunology panel. To validate the findings, changes in expression of key molecules of interest were also further investigated using qPCR, ELISA and immunocytochemistry. Type 1 Interferon signalling pathway was validated further using the Applied Biosystems™ TaqMan™ Array Human Interferon Pathway 96-well Plate arrays.
Results: The data reveals that DPSCs show differential immunomodulatory properties in response to E. coli LPS (TLR-4 agonist), PAM2CSK4 (TLR2/TLR6 agonist) and PAM3CSK4 (TLR2/TLR1 agonist). TLR-4 activation results in the expression of key immunomodulatory cytokines and chemokines (e.g., IL8, IL6, CCL2, CXCL1) via the MYD88 dependant signalling pathway. Moreover, TLR-4 activation specifically induces activation of the Type 1 Interferon signalling pathway.
Conclusions: The data shows that DPSCs have underappreciated immunomodulatory properties and play a role in the defence of dental pulp against microbial invasion. In addition, DPSCs may also play a role in inflammatory pain via a Type 1 interferon response. The findings reported therefore may allude to novel therapeutic targets to treat inflammatory or neuropathic pain.
Methods: A holistic approach to uncover the immunomodulatory properties of DPSCs was undertaken using NanostringTM technology. DPSCs were stimulated with Toll like receptor (TLR) ligands for 4 and 24 h and changes in levels of mRNA expression of 800 immunoregulatory molecules determined using the NanostringTM immunology panel. To validate the findings, changes in expression of key molecules of interest were also further investigated using qPCR, ELISA and immunocytochemistry. Type 1 Interferon signalling pathway was validated further using the Applied Biosystems™ TaqMan™ Array Human Interferon Pathway 96-well Plate arrays.
Results: The data reveals that DPSCs show differential immunomodulatory properties in response to E. coli LPS (TLR-4 agonist), PAM2CSK4 (TLR2/TLR6 agonist) and PAM3CSK4 (TLR2/TLR1 agonist). TLR-4 activation results in the expression of key immunomodulatory cytokines and chemokines (e.g., IL8, IL6, CCL2, CXCL1) via the MYD88 dependant signalling pathway. Moreover, TLR-4 activation specifically induces activation of the Type 1 Interferon signalling pathway.
Conclusions: The data shows that DPSCs have underappreciated immunomodulatory properties and play a role in the defence of dental pulp against microbial invasion. In addition, DPSCs may also play a role in inflammatory pain via a Type 1 interferon response. The findings reported therefore may allude to novel therapeutic targets to treat inflammatory or neuropathic pain.