Understanding the molecular basis of cell migration; implications for clinical therapy in multiple sclerosis

Clin Sci (Lond). 1997 Feb;92(2):113-22. doi: 10.1042/cs0920113.

Abstract

1. Multiple sclerosis is characterized by areas of demyelination spread throughout the central nervous system, in which the myelin sheaths surrounding axons are destroyed. While therapies aimed at suppressing the autoimmune response, such as beta-interferon, may prevent further damage, they cannot repair or replace the lost myelin. To this end, an additional therapy has been proposed, which involves transplanting cells of the oligodendrocyte lineage into the central nervous system. 2. The cell of interest for transplantation is the oligodendrocyte precursor because, unlike the differentiated cell, it is an intrinsically migratory and proliferative cell. In order to optimize the transplant strategy we have investigated the molecular mechanisms that control migration in vitro, so that these mechanisms might be upregulated to maximize cell migration in vivo. We have focused on the integrin family of cell adhesion molecules, known to play a fundamental role in the regulation of migration in other cell types. 3. These studies show that oligodendrocytes express a limited repertoire of integrins consisting of alpha 6 beta 1 and three different alpha v integrins. alpha 6 beta 1 is expressed throughout development but alpha v integrins show developmental regulation; differentiation is accompanied by loss of alpha v beta 1 and upregulation of alpha v beta 5. 4. Function-blocking studies show that oligodendrocyte precursor migration in vitro is mediated primarily by the developmentally regulated alpha v beta 1 integrin, but not alpha 6 beta 1 or alpha v beta 3. Taken together with previous evidence that cell migration can be regulated by altering integrin expression, this work suggests that modifying expression levels of alpha v beta 1 on oligodendrocyte precursors may increase the migratory capacity of these cells. If so, this would support a future therapeutic strategy aimed at transplanting genetically modified oligodendrocyte precursors to repair widespread demyelinated lesions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Movement / physiology
  • Central Nervous System / pathology
  • Humans
  • Integrins / analysis
  • Integrins / metabolism*
  • Mice
  • Multiple Sclerosis / therapy*
  • Myelin Sheath / physiology
  • Oligodendroglia / metabolism
  • Oligodendroglia / transplantation*
  • Rats
  • Receptors, Vitronectin*
  • Stem Cell Transplantation*
  • Stem Cells / metabolism

Substances

  • Integrins
  • Receptors, Vitronectin
  • integrin alphavbeta1