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

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109 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1254-1262
Number of pages9
JournalBrain
Volume130
Issue number5
DOIs
StatePublished - May 1 2007

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Keywords

  • Demyelination
  • Multiple sclerosis
  • Neurodegeneration
  • Stem cell transplantation

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Metz, I., Lucchinetti, C. F., Openshaw, H., Garcia-Merino, A., Lassmann, H., Freedman, M. S., Atkins, H. L., Azzarelli, B., Kolar, O. J., & Brück, W. (2007). Autologous haematopoietic stem cell transplantation fails to stop demyelination and neurodegeneration in multiple sclerosis. Brain, 130(5), 1254-1262. https://doi.org/10.1093/brain/awl370