Effect of subcutaneous treatment with human umbilical cord blood-derived multipotent stem cells on peripheral neuropathic pain in rats
Korean J Physiol Pharmacol 2017;21(2):153-160 https://doi.org/10.4196/kjpp.2017.21.2.153
Min Ju Lee1,#, Tae Gyoon Yoon2,#, Moonkyu Kang1, Hyun Jeong Kim1,*, and Kyung Sun Kang3,*
In this study, we aim to determine the in vivo 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.
In conclusion, our current study shows that transplantation of hUCB-MSCs is a novel strategy to relieve neuropathic pain, with potential as an alternative clinical therapy. However, further studies are required to determine clinical feasibility for long-term use to rule out adverse effects due to immune response.v