Article
Canine adipose tissue-derived mesenchymal stem cells show axonal protection in a viral model of multiple sclerosis
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Authors
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Florian Hansmann
- University of Veterinary Medicine Hannover, Department of Pathology, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany
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Nicole Jungwirth
- University of Veterinary Medicine Hannover, Department of Pathology, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany
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Ning Zhang
- University of Veterinary Medicine Hannover, Department of Pathology, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany
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Laura Salinas Tejedor
- Hannover Medical School, Department of Neurology, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany
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Thomas Skripuletz
- Hannover Medical School, Department of Neurology, Hannover, Germany
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Andrea Hoffmann
- Hannover Medical School, Department of Orthopaedic Surgery, Hannover, Germany
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Martin Stangel
- Hannover Medical School, Department of Neurology, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany
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Wolfgang Baumgärtner
- University of Veterinary Medicine Hannover, Department of Pathology, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany
| Published: | August 25, 2015 |
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Outline
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Introduction: Mesenchymal stem cells (MSC) are widely used in clinical practice and are supposed to exert regenerative properties. However, it is not well understood where and how long MSC reside in the host following transplantation. Accordingly, the observed therapeutic effects are maybe attributed directly to the transplanted cells or to their immunomodulatory properties e.g. by secreted factors.
Objectives: The present study investigated the impact of intra-cerebroventricularly or intra-venously administered MSC upon the progression of Theiler’s murine encephalomyelitis (TME)-induced demyelinating disease.
Materials & methods: Groups of 4-6 female, TME virus (TMEV)-infected SJL/J mice were intra-cerebroventricularly or intra-venously transplanted with 106 human or canine MSC at 7 or 42 days post infection (dpi). Histopathology and immunohistochemistry of cervical and thoracic spinal cord was performed at 14 and 56dpi (animals transplanted at 7dpi) as well as 49 and 98dpi (animals transplanted at 42dpi). For immunohistochemistry, antibodies targeting non-phosphorylated neurofilaments (axonal damage), CD3 (T lymphocytes), CD45R (B lymphocytes), CD107b (microglia/macrophages), myelin basic protein (demyelination) and TMEV were used.
Results: Intra-venous application of canine MSC at 7 days post TMEV infection was associated with increased numbers of microglia/macrophages and demyelination in the spinal cord at 56dpi. In contrast intra-venous application of canine MSC at 42dpi was associated with reduced axonal damage at 98dpi. Transplantation of human MSC at 42dpi via both routes reduced the degree of axonal damage at 98dpi.
Conclusion: A major difference regarding the time point as well as the route of MSC transplantation was observed. Intra-venously transplanted canine MSC behaved like a double edged sword with increased demyelination when administered at 7dpi, while transplantation of canine as well as human MSC at 42 dpi was associated with a reduced degree of axonal damage compared to non-transplanted mice at 98dpi. Whether the observed effects were directly attributed to the transplanted MSC or may be caused by a modulation of the immune response remains elusive.
