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Mesenchymal Stromal/Stem Cells Do Not Ameliorate Experimental Autoimmune Encephalomyelitis and Are Not Detectable in the Central Nervous System of Transplanted Mice

2016-06-07 15:28:20

Stem Cells and Development; 1 June 2016: DOI:10.1089/scd.2016.0020

Dr. Pierre Abramowski, Dr. Susanne Krasemann, Dr. Thomas Ernst, Dr. Claudia Lange, Dr. Harald Ittrich, Dr. Michaela Schweizer, Prof. Axel Zander, Prof. Roland Martin, and Dr. Boris Fehse



Abstract


Mesenchymal stromal/stem cells (MSCs) constitute progenitor cells that can be isolated from different tissues. Based on their immunomodulatory and neuroprotective functions, MSC-based cell-therapy approaches have been suggested to antagonize inflammatory activity and neuronal damage associated with autoimmune disease of the central nervous system (CNS), e.g. multiple sclerosis (MS). Intravenous MSC transplantation was reported to ameliorate experimental autoimmune encephalomyelitis (EAE), the murine model of MS, within days after transplantation. However, systemic distribution patterns and fate of MSCs after administration, especially their potential to migrate into inflammatory lesions within the CNS, remain to be elucidated. This question has of recent become particularly important, since therapeutic infusion of MSCs is now being tested in clinical trials with MS-affected patients. Here we made use of the established EAE mouse model to investigate migration and therapeutic efficacy of murine bone-marrow derived MSCs. Applying a variety of techniques, including magnetic-resonance imaging, immunohistochemistry, fluorescence in-situ hybridization, and quantitative PCR we found no evidence for immediate migration of infused MSC into the CNS of treated mice. Moreover, in contrast to other studies, transplanted MSCs did not ameliorate EAE. In conclusion, our data does not provide substantiation for a relevant migration of infused MSCs into the CNS of EAE mice supporting the hypothesis that potential therapeutic efficacy could be based on systemic effects. Evaluation of possible mechanisms underlying the observed discrepancies in MSC-treatment outcomes between different EAE models demands further studies.



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