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.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (NRF- 2011–0017276 ). The authors thank Professor Hosung Jung (Yonsei University College of Medicine) and Dr Jae Hwan Kim (Yonsei University College of Medicine) for their critical reading of the manuscript and assistance in revision. Disclosure of interests: The authors have no commercial, proprietary, or financial interest in the products or companies described in this article.
© 2015 International Society for Cellular Therapy.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Cell Biology
- Cancer Research