Abstract

The effects of stem cells from human exfoliated deciduous teeth (SHED) on mechanical allodynia were examined in mice. A single intravenous injection of SHED and conditioned medium from SHED (SHED-CM) through the left external jugular vein significantly reversed the established mechanical allodynia induced by spinal nerve transection at 6 days after injection. SHED or SHED-CM significantly decreased the mean numbers of activating transcription factor 3-positive neurons and macrophages in the ipsilateral side of the dorsal root ganglion (DRG) at 20 days after spinal nerve transection. SHED or SHED-CM also suppressed activation of microglia and astrocytes in the ipsilateral side of the dorsal spinal cord. A single intravenous injection of secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 had no effect on the established mechanical allodynia, whereas a single intravenous injection of protein component(s) contained in SHED-CM with molecular weight of between 30 and 50 kDa reversed the pain. Therefore, it may be concluded that protein component(s) with molecular mass of 30–50 kDa secreted by SHED could protect and/or repair DRG neurons damaged by nerve transection, thereby ameliorating mechanical allodynia.

Highlights

  • Stem cells from human exfoliated deciduous teeth (SHED) are thought to originate from the cranial neural crest with high self-renewal ability residing within the perivascular niche of the dental p­ ulp[1,2]

  • The present study has provided evidence that a single intravenous injection of either stem cells from human exfoliated deciduous teeth (SHED) or SHED-CM through the left external jugular vein reversed the established mechanical allodynia in mice

  • Our histological analyses here showed that a single intravenous injection of SHED or SHED-CM significantly reduced the mean number of AFT3-positive neurons and the accumulation of macrophages in the ipsilateral side of dorsal root ganglion (DRG)

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Summary

Introduction

Stem cells from human exfoliated deciduous teeth (SHED) are thought to originate from the cranial neural crest with high self-renewal ability residing within the perivascular niche of the dental p­ ulp[1,2]. Besides SHED, the conditioned serum-free medium from SHED (SHED-CM) exhibited tissue-repairing activities in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple s­ clerosis[10] and a rat model of spinal cord i­njury[11,12]. It is considered that mesenchymal stem cell-derived secreted factors directly convert the proinflammatory conditions prevalent in the damaged neurons to tissue-repairing ones by modulating the microglia/macrophage phenotype. Recent studies clarified the therapeutic significance of SHED in neuropathic pain caused by infraorbital nerve injury or diabetics in r­ ats[12,20,21]. We aimed to investigate the effects of SHED or SHED-CM on activated macrophage/microglia during neuropathic pain

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