Stem Cells from Human Exfoliated Deciduous Teeth Attenuate Trigeminal Neuralgia in Rats

Abstract

Trigeminal neuralgia is an incurable progressive nervous system disease that can last for several months or years. Stem cells from human exfoliated deciduous teeth (SHED) are a candidate source for cell-based therapy. Owing to their neuroprotective and immunomodulatory effects, these neural crest cells have potential roles in mediating chronic pain. In this study, we established a rat model of chronic constriction injury of the infraorbital nerve (CCI-ION) to evaluate the analgesic effect of SHED in neuropathic pain. The effects of local SHED transplantation on inflammatory cell infiltration in the trigeminal nerve were investigated based on hematoxylin and eosin staining. The levels of proinflammatory factors in the injured nerve and transient receptor potential vanilloid type 1 (TRPV1) expression in the trigeminal nerve and ganglion were quantified. The data showed that systemic or local injection of SHED attenuated the sensitivity of rats to mechanical stimuli after nerve injury, and this effect lasted throughout the observation period of 8 weeks. PKH26-labeled SHED were distributed to the ipsilateral trigeminal ganglions 24 and 72 hours after local injection. SHED transplantation at the lesion site led to reduced inflammatory cell infiltration and proinflammatory cytokine levels in the injured nerve and inhibited CCI-ION-induced upregulation of TRPV1 expression in the trigeminal nerve and ganglion in the early phase. Therefore, these results provide preclinical evidence that supports the use of SHED in the treatment of trigeminal neuralgia and potentially other chronic pain conditions.

Stem cells from human exfoliated deciduous teeth attenuate mechanical allodynia in mice through distinct from the siglec-9/MCP-1-mediated tissue-repairing mechanism

“…Consistent with the present observations, a single intraspinal administration of SHED-CM loaded in collagen hydrogel showed anti-allodynic effects in the spinal cord injury model in rats 12 . In addition, the mean head withdrawal threshold in rats with infraorbital nerve ligation was significantly increased by a single systemic or local injection of SHED 20 . Accordingly, SHED has a potential therapeutic effect on severe neuropathic pain in animals.…”

“…However, 6-CFDA-labeled SHED selectively migrated in the damaged site but not in the intact site, and anti-allodynic effects of SHED lasted for 20 days. After SHED administration, SHED migrated into the injured but not the intact side of the trigeminal ganglion after infraorbital nerve injury (a model of orofacial neuropathic pain) in rats 20 . Furthermore, the anti-allodynic effects of SHED lasted for 8 weeks 20 .…”

“…After SHED administration, SHED migrated into the injured but not the intact side of the trigeminal ganglion after infraorbital nerve injury (a model of orofacial neuropathic pain) in rats 20 . Furthermore, the anti-allodynic effects of SHED lasted for 8 weeks 20 . Accordingly, long-lasting anti-allodynic effects might be observed in our case.…”

“…Thus, the importance of activated macrophages/microglia has been implicated in intractable neuropathic pain. Recent studies clarified the therapeutic significance of SHED in neuropathic pain caused by infraorbital nerve injury or diabetics in rats 12 , 20 , 21 . Analgesic mechanisms by SHED administration are revealed that SHED suppresses the upregulation of transient receptor potential vanilloid type 1 (TRPV1) in trigeminal ganglion neurons following infraorbital nerve injury 20 .…”

Stem Cells From Human Exfoliated Deciduous Teeth Attenuate Trigeminal Neuralgia in Rats By Inhibiting Endoplasmic Reticulum Stress

“…Given the neurogenic differentiation in vivo and neural crest origin of SHED, they provide an alternative model for treating chronic pain, including TN. We previously showed that SHED are crucially involved in attenuating TN; however, the underlying mechanisms remain unclear (Bai et al 2021b).…”