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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*
Department of Veterinary surgery, College of Veterinary Medicine, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea
Correspondence to: 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 1, 2016.
Abstract
Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that modulate immune response and oxidative stress associated with spinal cord injury (SCI). This study aimed to investigate neuronal regeneration by transplantation of mesenchymal stromal cells (MSCs) overexpressing HO-1. Canine MSCs overexpressing HO-1 were generated using a lentivirus packaging protocol. Eight beagle dogs with experimentally-induced SCI were GFP-labeled MSCs (MSC-GFP) and HO-1 overexpressed MSCs (MSC-HO-1) groups. MSCs (1 × 107 cells) were transplanted at 1 week after SCI. The spinal cords were harvested 8 weeks after transplantation, following which histopathological, immunofluorescence, and western blot analyses were performed. MSC-HO-1 group showed significantly improved functional recovery 7 weeks after transplantation. Histopathological analysis with H&E staining showed fibrotic changes and infiltration of microglial cells that were significantly decreased in the MSC-HO-1 group. Immunohistochemistry (IHC) revealed that expression levels of HO-1 and neuronal markers were higher in the MSC-HO-1 group. Western blot showed significantly decreased expression of TNFα, IL6, COX2, p-STAT3, and GALC in the MSC-HO-1 group and expression levels of GFAP, β3-tubulin, NF-M, and NeuN revealed similar to those observed in IHC analysis. Our results demonstrated that functional recovery after SCI was promoted by transplantation of MSCs overexpressing HO-1 than that of MSCs.
Keywords: anti-inflammatory, anti-oxidant, heme oxygenase-1, mesenchymal stromal cells, spinal cord injury


© 2016 The Korean Society of Veterinary Science.