Restorative benefits of transplanting human mesenchymal stromal cells overexpressing arginine decarboxylase genes after spinal cord injury

Yu Mi Park, Sun Hyup Han, Su Kyung Seo, Kyung Ah Park, Won Taek Lee, Jong Eun Lee

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 1mm 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.

Original languageEnglish
Pages (from-to)25-37
Number of pages13
JournalCytotherapy
Volume17
Issue number1
DOIs
Publication statusPublished - 2015 Jan 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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