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Early Immunomodulation by Intravenously Transplanted Mesenchymal Stem Cells Promotes Functional Recovery in Spinal Cord Injured Rats

 Seo, Jung Hwa  ;  Jang, In Keun  ;  Cho, Sung-Rae  ;  Kim, Hyun Ok  ;  Kim, Ji Yeon  ;  Yu, Ji Hea  ;  Lee, Doo-Hoon  ;  Eom, Yong-Woo  ;  Kim, Hyo Eun  ;  Lee, Jong Eun  ;  Yang, Mal Sook  ;  Kim, Hyongbum 
 Cell Medicine, Part B of Cell Transplantation, Vol.2(2) : 55-67, 2011 
Journal Title
 Cell Medicine, Part B of Cell Transplantation 
Issue Date
Although intravenous administration of mesenchymal stem cells (MSCs) can enhance functional recovery after spinal cord injury (SCI), the underlying mechanisms have to be elucidated. In this study, we explored the mechanisms for functional recovery in SCI rats after intravenous transplantation of MSCs derived from human umbilical cord blood. Sprague-Dawley rats were randomly assigned to receive either MSCs (1 × 106 cells/0.5 ml) or PBS into the tail vein immediately after SCI. They were then evaluated by the Basso-Beattie-Bresnahan (BBB) locomotor rating scale weekly for 8 weeks and by somatosensory evoked potentials (SSEPs) 8 weeks after transplantation. MSC-treated rats showed a modest but significant improvement in BBB scores and latencies of SSEPs, compared with PBS controls. When human-specific Alu element was measured in the spinal cord, it was detected only 1 h after transplantation, suggesting transient engraftment of MSCs. Inflammatory cytokines were also determined using RT-PCR or Western blot in spinal cord extracts. In MSC-treated rats, the level of proinflammatory cytokine IL-1β was decreased, but that of anti-inflammatory cytokine IL-10 was increased. MSCs also immediately suppressed IL-6 at 1 h posttransplantation. However, the response of IL-6, which has an immunoregulatory role, was increased 1‐3 days after transplantation. In addition, we quantified microglia/macrophage stained with Iba-1 around the damaged spinal cord using immunohistochemistry. A proportion of activated microglia and macrophages in total Iba-1+ cells was significantly decreased in MSC-treated rats, compared with PBS controls. These results suggest that early immunomodulation by intravenously transplanted MSCs is a potential underlying mechanism for functional recovery after SCI.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실)
Yonsei Authors
김지연(Kim, Ji Yeon) ; 김현옥(Kim, Hyun Ok) ; 서정화(Seo, Jung Hwa) ; 유지혜(Yu, Ji Hea) ; 조성래(Cho, Sung Rae)
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