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J Vet Sci 2017; 18(3): 377-386  https://doi.org/10.4142/jvs.2017.18.3.377
Effect of canine mesenchymal stromal cells overexpressing heme oxygenase-1 in spinal cord injury
Seung Hoon Lee, Yongsun Kim, Daeun Rhew, Ahyoung Kim, Kwang Rae Jo, Yongseok Yoon, Kyeung Uk Choi, Taeseong Jung, Wan Hee Kim, Oh-Kyeong Kweon*
BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08872, Korea
Correspondence to: Oh-Kyeong Kweon
Tel: +82-2-880-1248; Fax: +82-2-888-2866; E-mail: ohkweon@snu.ac.kr
Received: March 23, 2016; Revised: July 4, 2016; Accepted: August 26, 2016; Published online: September 30, 2017.
Abstract
Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that modulates the immune response and oxidative stress associated with spinal cord injury (SCI). This study aimed to investigate neuronal regeneration via transplantation of mesenchymal stromal cells (MSCs) overexpressing HO-1. Canine MSCs overexpressing HO-1 were generated by using a lentivirus packaging protocol. Eight beagle dogs with experimentally-induced SCI were divided into GFP-labeled MSC (MSC-GFP) and HO-1-overexpressing MSC (MSC-HO-1) groups. MSCs (1 × 107 cells) were transplanted at 1 week after SCI. Spinal cords were harvested 8 weeks after transplantation, after which histopathological, immunofluorescence, and western blot analyses were performed. The MSC-HO-1 group showed significantly improved functional recovery at 7 weeks after transplantation. Histopathological results showed fibrotic changes and microglial cell infiltration were significantly decreased in the MSC-HO-1 group. Immunohistochemical (IHC) results showed significantly increased expression levels of HO-1 and neuronal markers in the MSC-HO-1 group. Western blot results showed significantly decreased expression of tumor necrosis factor-alpha, interleukin-6, cycloogygenase 2, phosphorylated-signal transducer and activator of transcription 3, and galactosylceramidase in the MSC-HO-1 group, while expression levels of glial fibrillary acidic protein, β3-tubulin, neurofilament medium, and neuronal nuclear antigen were similar to those observed in IHC results. Our results demonstrate that functional recovery after SCI can be promoted to a greater extent by transplantation of HO-1-overexpressing MSCs than by normal MSCs.
Keywords: heme oxygenase-1, mesenchymal stromal cells, spinal cord injuries


© 2017 The Korean Society of Veterinary Science.