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  • Title: Restorative benefits of transplanting human mesenchymal stromal cells overexpressing arginine decarboxylase genes after spinal cord injury.
    Author: Park YM, Han SH, Seo SK, Park KA, Lee WT, Lee JE.
    Journal: Cytotherapy; 2015 Jan; 17(1):25-37. PubMed ID: 25442787.
    Abstract:
    BACKGROUND AIMS: 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.
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