Korean J Physiol Pharmacol.  2017 Mar;21(2):153-160. 10.4196/kjpp.2017.21.2.153.

Effect of subcutaneous treatment with human umbilical cord blood-derived multipotent stem cells on peripheral neuropathic pain in rats

Affiliations
  • 1Department of Dental Anesthesiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 03080, Korea. dentane@snu.ac.kr
  • 2Department of Anesthesiology and Pain Medicine, Konkuk University Medical Center, Research Institute of Medical Science, Konkuk University School of Medicine, Seoul 05030, Korea.
  • 3Adult Stem Cell Research Center, Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea. kangpub@snu.ac.kr

Abstract

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.

Keyword

Cord blood stem cell transplantation; Neuropathic pain; Rat subcutaneous injection; Tissue inhibitor of metalloproteinase 2
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