Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats

Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats
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DOI:
10.1007/s11064-016-2051-5
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发表时间:
2016-12-01
影响因子:
4.4
通讯作者:
Chen, Xiangdong
Chen, Xiangdong
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Chunxiu;Chen, Fengfeng;Chen, Xiangdong

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神经性疼痛(NP)是一种病因多、机制复杂、现有治疗方法疗效不佳的临床不治之症。最近的一些研究表明,神经炎症在NP的发生和促进中起着至关重要的作用,抗炎治疗具有减轻疼痛的潜力。近几十年来,间充质干细胞(mesenchymal stem cells, MSCs)具有多能性、低免疫原性和抗炎活性等特点,在细胞治疗中从动物模型到临床应用均表现出优异的治疗效果,引起了人们的广泛关注。然而,鞘内人脐带间充质干细胞(HUC-MSCs)对周围神经损伤所致NP的影响尚未见报道。因此,本研究通过鞘内移植HUC-MSCs对脊髓神经结扎(SNL)大鼠模型神经性疼痛的影响,探讨其可能的作用机制。结果显示,HUC-MSCs移植能明显改善snl诱导的机械性异常痛和热痛觉过敏,这与神经炎症的抑制过程有关,包括活化的星形胶质细胞和小胶质细胞的抑制,以及促炎细胞因子白细胞介素-1 β (IL-1 β)和白细胞介素-17A (IL-17A)的显著降低和抗炎细胞因子白细胞介素-10 (IL-10)的上调。因此,通过对神经胶质细胞、促炎和抗炎细胞因子的作用,靶向鞘内HUC-MSCs可能为NP提供一种新的治疗策略。
Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti-inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1 beta (IL-1 beta) and Interleukin -17A (IL-17A) and the up-regulation of anti-inflammatory cytokine Interleukin -10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti-inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP.