Abstract
For the treatment of patients with multiple sclerosis there are no regenerative approaches to enhance remyelination. Mesenchymal stem cells (MSC) have been proposed to exert such regenerative functions. Intravenous administration of human MSC reduced the clinical severity of experimental autoimmune encephalomyelitis (EAE), an animal model mimicking some aspects of multiple sclerosis. However, it is not clear if this effect was achieved by systemic immunomodulation or if there is an active neuroregeneration in the central nervous system (CNS). In order to investigate remyelination and regeneration in the CNS we analysed the effects of intravenously and intranasally applied murine and human bone marrow-derived MSC on cuprizone induced demyelination, a toxic animal model which allows analysis of remyelination without the influence of the peripheral immune system. In contrast to EAE no effects of MSC on de- and remyelination and glial cell reactions were found. In addition, neither murine nor human MSC entered the lesions in the CNS in this toxic model. In conclusion, MSC are not directed into CNS lesions in the cuprizone model where the blood-brain-barrier is intact and thus cannot provide support for regenerative processes.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that affects mostly young adults [1]
No effect of human and mouse Mesenchymal stem cells (MSC) on demyelination To analyse the effects of human and mouse MSC on cuprizone induced demyelination two different administration routes were investigated
Mice fed with normal chow and treated i.n. and i.v. with human or murine MSC showed a physiological myelination in the corpus callosum with an intact structure
Summary
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that affects mostly young adults [1] It leads to focal inflammatory demyelination, gliosis, and axonal damage. Despite the potential to differentiate into different cell types many effects of MSC are thought to be mediated by creating an environment that forms the basis for the recruitment and stimulation of cells which are required for successful remyelination. These effects might be driven directly or might result from a modulation of the peripheral immune system [15]. In healthy animals i.v. injected MSC were found predominantly in the lungs and only few MSC were found in the brain and spinal cord [19,21,22,23]
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