title: Restorative benefits of transplanting human mesenchymal stromal cells overexpressing arginine decarboxylase genes after spinal cord injury.
abstract: OBJECTIVE
  Mesenchymal stromal cells (MSCs) promote functional recovery in central nervous system (CNS) injury. Neuroprotective effects of MSCs are being tested in clinical trials for the treatment of CNS injury; however, the underlying mechanisms remain unclear. Arginine decarboxylase (ADC) is a rate-limiting enzyme of agmatine synthesis and is known to exist in the CNS of mammals. The present study investigated whether transplantation of ADC-overexpressing human MSCs (ADC-hMSCs) after spinal cord injury (SCI) could increase the production of neurotrophic factors and promote cell survival, differentiation, axonal regeneration and the restoration of functional recovery.
  
  
  METHODS
  Retroviral human ADC was constructed with the use of an LXSN vector. After compression injury in thoracic level 9, PKH26-labeled ADC-hMSCs were transplanted into the dorsolateral funiculus 1 mm rostral and caudal to the lesion site. The tissues were sampled at 2, 4 and 10 weeks after SCI.
  
  
  RESULTS
  Behavioral analysis revealed that locomotor functions of the ADC-hMSC group were significantly restored. Histological analysis showed that the fibrotic scar volume was smaller in the ADC-hMSC-injected group than in any other group. Brain-derived neurotrophic factor level was significantly higher in the ADC-hMSC-injected group than in any other group throughout 10 weeks. Terminal deoxynucleotidyl transferase-mediated nick-end labeling assay showed decreased cell death, and co-localization analysis showed significant increase in the number of neurons and oligodendrocytes originating from transplanted hMSCs when they had been transduced with the ADC gene.
  
  
  CONCLUSIONS
  The results suggested that ADC-hMSCs are a more suitable candidate than hMSCs for stem cell therapy after SCI.
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yu Mi
authors.initials: YM
authors.lastname: Park
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sun Hyup
authors.initials: SH
authors.lastname: Han
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Su Kyung
authors.initials: SK
authors.lastname: Seo
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyung Ah
authors.initials: KA
authors.lastname: Park
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Won Taek
authors.initials: WT
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Yonsei University College of Medicine, Seoul, Republic of Korea; BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: jelee@yuhs.ac.
authors.forename: Jong Eun
authors.initials: JE
authors.lastname: Lee
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*
chemical_list: D002262:Carboxy-Lyases; C019722:arginine decarboxylase
keywords: arginine decarboxylase; mesenchymal stromal cells; spinal cord injury; transplantation