Lee Min Ju, Yoon Tae Gyoon, Kang Moonkyu, Kim Hyun Jeong, Kang Kyung Sun
Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Korea.
Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul 05030, Korea.
Korean J Physiol Pharmacol. 2017 Mar;21(2):153-160. doi: 10.4196/kjpp.2017.21.2.153. Epub 2017 Feb 21.
In this study, we aim to determine the effect of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) on neuropathic pain, using three, principal peripheral neuropathic pain models. Four weeks after hUCB-MSC transplantation, we observed significant antinociceptive effect in hUCB-MSC-transplanted rats compared to that in the vehicle-treated control. Spinal cord cells positive for c-fos, CGRP, p-ERK, p-p 38, MMP-9 and MMP 2 were significantly decreased in only CCI model of hUCB-MSCs-grafted rats, while spinal cord cells positive for CGRP, p-ERK and MMP-2 significantly decreased in SNL model of hUCB-MSCs-grafted rats and spinal cord cells positive for CGRP and MMP-2 significantly decreased in SNI model of hUCB-MSCs-grafted rats, compared to the control 4 weeks or 8weeks after transplantation (p<0.05). However, cells positive for TIMP-2, an endogenous tissue inhibitor of MMP-2, were significantly increased in SNL and SNI models of hUCB-MSCs-grafted rats. Taken together, subcutaneous injection of hUCB-MSCs may have an antinociceptive effect via modulation of pain signaling during pain signal processing within the nervous system, especially for CCI model. Thus, subcutaneous administration of hUCB-MSCs might be beneficial for improving those patients suffering from neuropathic pain by decreasing neuropathic pain activation factors, while increasing neuropathic pain inhibition factor.
在本研究中，我们旨在使用三种主要的外周神经性疼痛模型，确定人脐带血源性多能干细胞（hUCB-MSCs）对神经性疼痛的影响。hUCB-MSC移植四周后，我们观察到与载体处理的对照组相比，hUCB-MSC移植大鼠有显著的镇痛作用。仅在hUCB-MSCs移植大鼠的CCI模型中，c-fos、CGRP、p-ERK、p-p38、MMP-9和MMP2阳性的脊髓细胞显著减少，而在hUCB-MSCs移植大鼠的SNL模型中，CGRP、p-ERK和MMP-2阳性的脊髓细胞显著减少，在hUCB-MSCs移植大鼠的SNI模型中，CGRP和MMP-2阳性的脊髓细胞与移植后4周或8周的对照组相比显著减少（p<0.05）。然而，在hUCB-MSCs移植大鼠的SNL和SNI模型中，MMP-2的内源性组织抑制剂TIMP-2阳性的细胞显著增加。综上所述，皮下注射hUCB-MSCs可能通过在神经系统内疼痛信号处理过程中调节疼痛信号而产生镇痛作用，尤其是对于CCI模型。因此，皮下给予hUCB-MSCs可能有利于改善那些患有神经性疼痛的患者，通过减少神经性疼痛激活因子，同时增加神经性疼痛抑制因子。
