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

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Abstract:

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.

Keywords: Functional recovery; Immunomodulation; Mesenchymal stem cells (MSCs); Spinal cord injury; Transplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/215517911X582788

Publication date: February 1, 2011

More about this publication?
  • The importance of translating original, peer-reviewed research and review articles on the subject of cell therapy and its application to human diseases to society has led to the formation of the journal Cell Medicine. To ensure high-quality contributions from all areas of transplantation, the same rigorous peer review will be applied to articles published in Cell Medicine. Articles may deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, and stem cells, among others. Basic clinical studies and immunological research papers may also be featured if they have a translational interest. To provide complete coverage of this revolutionary field, Cell Medicine will report on relevant technological advances and their potential for translational medicine. Cell Medicine will be a purely online Open Access journal. There will therefore be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow your work to be disseminated to a wider audience and also entitle you to a free PDF, as well as prepublication of an unedited version of your manuscript.
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