title: Transplantation of human umbilical cord blood or amniotic epithelial stem cells alleviates mechanical allodynia after spinal cord injury in rats.
abstract: Stem cell therapy is a potential treatment for spinal cord injury (SCI), and a variety of different stem cell types have been grafted into humans suffering from spinal cord trauma or into animal models of spinal injury. Although several studies have reported functional motor improvement after transplantation of stem cells into injured spinal cord, the benefit of these cells for treating SCI-induced neuropathic pain is not clear. In this study, we investigated the therapeutic effect of transplanting human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) or amniotic epithelial stem cells (hAESCs) on SCI-induced mechanical allodynia (MA) and thermal hyperalgesia (TH) in T13 spinal cord hemisected rats. Two weeks after SCI, hUCB-MSCs or hAESCs were transplanted around the spinal cord lesion site, and behavioral tests were performed to evaluate changes in SCI-induced MA and TH. Immunohistochemical and Western blot analyses were also performed to evaluate possible therapeutic effects on SCI-induced inflammation and the nociceptive-related phosphorylation of the NMDA NR1 receptor subunit. While transplantation of hUCB-MSCs showed a tendency to reduce MA, transplantation of hAESCs significantly reduced MA. Neither hUCB-MSC nor hAESC transplantation had any effect on SCI-induced TH. Transplantation of hAESCs also significantly reduced the SCI-induced increase in NMDA receptor NR1 subunit phosphorylation (pNR1) expression in the spinal cord. Both hUCB-MSCs and hAESCs reduced the SCI-induced increase in spinal cord expression of the microglial marker, F4/80, but not the increased expression of GFAP or iNOS. Taken together, these findings demonstrate that the transplantation of hAESCs into the injured spinal cord can suppress mechanical allodynia, and this effect seems to be closely associated with the modulation of spinal cord microglia activity and NR1 phosphorylation.
authors.affiliation: Department of Maxillofacial Tissue Regeneration, School of Dentistry, Kyung Hee University, Seoul, South Korea.
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Roh
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Seo
authors.forename: Hoon-Seong
authors.initials: HS
authors.lastname: Choi
authors.forename: Sang-Bum
authors.initials: SB
authors.lastname: Park
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Alvin J
authors.initials: AJ
authors.lastname: Beitz
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Jang-Hern
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000650:Amnion / Q000166:cytology* / Q000378:metabolism; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000637:transplantation; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D013119:Spinal Cord Injuries / Q000150:complications / Q000601:surgery*