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

Imke Metz , Claudia F. Lucchinetti , Harry Openshaw , Antonio Garcia-Merino , Hans Lassmann , Marc S. Freedman , Harold L. Atkins , Biagio Azzarelli , Oldrich J. Kolar , Wolfgang Brück
DOI: http://dx.doi.org/10.1093/brain/awl370 1254-1262 First published online: 9 February 2007

Summary

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.

  • multiple sclerosis
  • stem cell transplantation
  • demyelination
  • neurodegeneration
  • Abbreviations:
    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
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