title: Mesenchymal Stromal/Stem Cells Do Not Ameliorate Experimental Autoimmune Encephalomyelitis and Are Not Detectable in the Central Nervous System of Transplanted Mice.
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), for example, 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 polymerase chain reaction 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.
authors.affiliation: 1 Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .|2 Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (INIMS), ZMNH, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Pierre
authors.initials: P
authors.lastname: Abramowski
authors.affiliation: 3 Institute for Neuropathology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.affiliation: 4 Diagnostic and Interventional Radiology Department and Clinic, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.affiliation: 1 Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Claudia
authors.initials: C
authors.lastname: Lange
authors.affiliation: 4 Diagnostic and Interventional Radiology Department and Clinic, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Harald
authors.initials: H
authors.lastname: Ittrich
authors.affiliation: 5 Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Michaela
authors.initials: M
authors.lastname: Schweizer
authors.affiliation: 6 Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Axel R
authors.initials: AR
authors.lastname: Zander
authors.affiliation: 2 Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (INIMS), ZMNH, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .|7 Neuroimmunology and MS Research, Department of Neurology, University Hospital Zurich , Zurich, Switzerland .
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.affiliation: 1 Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
authors.forename: Boris
authors.initials: B
authors.lastname: Fehse
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000473:pathology*; D003911:Dextrans / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000628:therapy*; D008099:Liver / Q000166:cytology; D008168:Lung / Q000166:cytology; D058185:Magnetite Nanoparticles; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; C065507:ferumoxides