Evaluation of mesenchymal stem cell modulation of trigeminal neuronal responses to cold

Michael A. Eskander, Koyo Takimoto, Anibal Diogenes

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)61-67
Number of pages7
StatePublished - Sep 30 2017


  • ATP
  • TRPA1
  • TRPM8
  • apical papilla
  • mesenchymal stem cells
  • regenerative endodontics

ASJC Scopus subject areas

  • General Neuroscience


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