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Brain Advance Access originally published online on February 9, 2007
Brain 2007 130(5):1254-1262; doi:10.1093/brain/awl370
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis

Imke Metz1, Claudia F. Lucchinetti2, Harry Openshaw3, Antonio Garcia-Merino4, Hans Lassmann5, Marc S. Freedman6, Harold L. Atkins6, Biagio Azzarelli7, Oldrich J. Kolar7 and Wolfgang Brück1,8

1Department of Neuropathology, Georg August University, Göttingen, Germany, 2Department of Neurology, Mayo Clinic, College of Medicine, Rochester, MN, 3Department of Neurology, City of Hope National Medical Center, Duarte, CA, USA, 4Servicio de Neurologia, Clinica Puerta de Hierro, Universidad Autonoma, Madrid, Spain, 5Center for Brain Research, Medical University of Vienna, Austria, 6Department of Medicine, University of Ottawa, The Ottawa Hospital Research Institute, Ottawa, ON, Canada, 7Indiana University School of Medicine, Indiana University, Indianapolis, IN, USA and 8Institut für Multiple-Sklerose-Forschung, Bereich Humanmedizin der Universität Göttingen und Gemeinnützige Hertie-Stiftung, Göttingen, Germany

Correspondence to: Prof. Wolfgang Brück, MD, Institut für Neuropathologie, Georg-August-Universität Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany E-mail: wbrueck{at}med.uni-goettingen.de

The present study analyses autopsy material from five multiple sclerosis patients who received autologous stem cell transplantation. A total of 53 white matter lesions were investigated using routine and immunohistochemical stainings to characterize the demyelinating activity, inflammatory infiltrates, acutely damaged axons and macrophages/microglial cells. We found evidence for ongoing active demyelination in all of the five patients. The inflammatory infiltrate within the lesions showed only very few T cells and CD8+ cytotoxic T cells dominated the T cell population. B cells and plasma cells were completely absent from the lesions. High numbers of acutely damaged axons were found in active lesion areas. Tissue injury was associated with activated macrophages/microglial cells. The present results indicate that ongoing demyelination and axonal degeneration exist despite pronounced immunosuppression. Our data parallel results from some of the clinical phase I/II studies showing continued clinical disease progression in multiple sclerosis patients with high expanded disability system scores despite autologous stem cell transplantation.

Key Words: multiple sclerosis; stem cell transplantation; demyelination; neurodegeneration

Abbreviations: APP, amyloid precursor protein; ASCT, autologous stem cell transplantation; BMT, bone marrow transplantation; EDSS, Expanded Disability Status Scale; EAE, experimental allergic encephalomyelitis; HSCT, haematopoietic stem cell transplantation

Received October 9, 2006. Revised November 30, 2006. Accepted December 5, 2006.


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