Abstract

Neuropathic pain caused by lesions or nervous system dysfunction is a neuroimmune disease with limited therapeutic options. Adipose tissue-derived stem cells (ASCs) are multipotent mesenchymal stem cells with potent immunosuppressive properties, and their use as novel cell-based therapeutics have been proposed in many immune diseases. However, the analgesic effect and efficacy of ASCs to treat neuropathic pain remain unclear. This study, thus, investigated whether ASCs or ASC-derived culture medium can relieve neuropathic pain behaviors (i.e., mechanical and cold allodynia) in a rat model with L5 spinal nerve ligation. Intrathecal injection of ASCs significantly reduced cold allodynia, but not mechanical allodynia. Importantly, cold allodynia was completely reversed in rats with repeated injections of ASCs. In contrast, intrathecal injection of ASC-derived culture medium or retro-orbital injection of ASCs had no effect on neuropathic pain behaviors. These results suggest a novel and alternative therapeutic application of ASCs to target specific neuropathic pain behaviors.

Highlights

  • Current therapies for neuropathic pain are inadequate, with low efficacy and detrimental side effects

  • We validated the Adipose tissue-derived stem cell (ASC) for four passages (see Figure 1(a)) by fluorescent immunostaining for CD105, CD54, CD44

  • Comparing with controls using isotype-matched fluorescein isothiocyanate- (FITC-)conjugated antibodies, we found that the cultured ASCs were positive for CD105 (80.25%), CD44 (80.34%), and CD45 (44.50%), and that only 1.87% of the cells were positive for CD45 (see Figure 1(b))

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Summary

Introduction

Current therapies for neuropathic pain are inadequate, with low efficacy and detrimental side effects. Most of these therapies target pain transduction and transmission in the neurons, it is clear that neuropathic pain is a neuroimmune [1]. New immune-based therapies have been tested to treat neuropathic pain, including mesenchymal stem cells (MSCs) [2]. Adipose tissue-derived stem cells (ASCs) are multipotent mesenchymal stem cells, similar to bone marrow-derived stem cells, and can differentiate into various cell types, including osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic cells, and hepatocytes [4]. ASCs are considered one of the most promising cell types for cell-based therapies in cases of tissue failure, immune diseases, and neuronal pathologies. The effect and efficacy of ASCs for relieving and treating neuropathic pain remain unclear

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