Evaluation of mesenchymal stem cell modulation of trigeminal neuronal responses to cold. (30th September 2017)

• Record Type: Journal Article
• Authors: Eskander, Michael A.; Takimoto, Koyo; Diogenes, Anibal
• Is Part Of: Neuroscience. Volume 360(2017)
• Page Start: 61
• Page End: 67
• Publication Date: 2017-09-30
• Subjects: EGTA ethylene glycol-bis(β-aminoethyl ether)-N, N, N′, N′-tetraacetic acid -- Hepes 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- MSCs mesenchymal stem cells -- NGF nerve growth factor -- REPs regenerative endodontic procedures -- SCAP stem cells of the apical papilla -- TG trigeminal -- TRPA1 transient receptor potential ankyrin type 1 -- TRPM8 transient receptor potential melastatin 8; mesenchymal stem cells -- regenerative endodontics -- TRPA1 -- TRPM8 -- ATP -- apical papilla; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.07.050
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Cold stimulus to teeth reaches the activation threshold for TRPA1 and TRPM8. TRPA1- and TRPM8- and ATP-mediated inward currents in trigeminal neurons are enhanced by SCAP co-culture. Conditioned media from SCAP exposed to 15 °C activate P2X3 and/or P2X2/3 in trigeminal neurons. Abstract: Tissue engineering protocols, such as regenerative endodontic procedures (REPs), comprise biologically based procedures designed to restore normal physiologic function. For REPs, the goal is reconstitution of the pulp-dentin complex by delivering mesenchymal stem cells (MSCs), including the stem cells of the apical papilla (SCAP) into a root canal system. Many patients regain cold sensitivity after REPs, but the mechanism is not understood. We hypothesized that SCAP modulate nociceptive function through a paracrine mechanism that activates cold-sensitive ion channels in neurons. We established a co-culture system with human SCAP and rat trigeminal (TG) sensory neurons in order to determine the effect of SCAP co-culture on neuronal responses using whole-cell patch-clamp electrophysiology. TG neurons co-cultured with SCAP demonstrated increased TRPA1-mediated ( p < 0.01) and TRPM8-mediated inward current densities ( p < 0.01) at 24 h in co-culture. Cold stimulation to SCAP significantly increased ATP release ( p < 0.01), and supernatant collected after cold stimulation to SCAP was able to activate cultured TG neurons. Co-culture with SCAP significantly increased sustained ATP-evoked inward current density ( p < 0.05). These data suggest that SCAP release trophic factors that act on afferent neurons to enhance cold-sensitive ion channel activity.