Oligodendrocyte progenitor cell susceptibility to injury in multiple sclerosis

Qiao-Ling Cui, Tanja Kuhlmann, Veronique E Miron, Soo Yuen Leong, Jun Fang, Pavel Gris, Timothy E Kennedy, Guillermina Almazan, Jack Antel

Research output: Contribution to journalArticlepeer-review


Remyelination in multiple sclerosis (MS) is often incomplete. In experimental models, oligodendrocyte progenitor cells (OPCs) rather than previously myelinating oligodendrocytes (OLs) are responsible for remyelination. This study compares the relative susceptibility of adult human OPCs and mature OLs to injury in actively demyelinating MS lesions and under in vitro stress conditions. In all lesions (n = 20), the number of OLs (Olig2 weak/NogoA positive) was reduced compared to control white matter (mean 38 ± 4% of control value). In 11 cases, OPC numbers (Olig2 strong; NogoA negative) were also decreased; in eight of these, the reduction was greater for OPCs than for OLs. In the other nine samples, OPC numbers were greater than control white matter, indicating ongoing OPC migration and/or proliferation. Analysis of co-cultures with rat dorsal root ganglia neurons confirmed that OPCs were more capable of contacting and ensheathing axons than OLs. In isolated culture under stress conditions (withdrawal of serum/glucose and/or antioxidants), OPCs showed increased cell death and reduced process extension compared to OLs. Under all culture conditions, OPCs up-regulated expression of genes in the extrinsic proapoptotic pathway, and had increased susceptibility to tumor necrosis factor-induced cell death as compared to OLs. Our data suggest that susceptibility of OPCs to injury within the MS lesion environment contributes to the limited remyelination in MS.

Original languageEnglish
Pages (from-to)516-25
Number of pages10
JournalThe American Journal of Pathology
Issue number2
Publication statusPublished - Aug 2013


  • Adult
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Axons
  • Basic Helix-Loop-Helix Transcription Factors
  • Cells, Cultured
  • Disease Susceptibility
  • Ganglia, Spinal
  • Humans
  • Multiple Sclerosis
  • Myelin Sheath
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Nerve Regeneration
  • Nerve Tissue Proteins
  • Oligodendroglia
  • Rats
  • Stem Cells


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