chapter  4
10 Pages

Growth factors, lesion repair and myelin regeneration

ByHenry deF Webster

Growth factors (GFs) are multifunctional, hormone-like proteins with receptor-mediated actions. There is now substantial in vitro and in vivo evidence that a number of GFs have effects on the proliferation, differentiation and survival of oligodendroglia, the cells that form, maintain and regenerate CNS myelin.1-5 These effects and the occurrence of myelin breakdown in multiple sclerosis (MS) lesions led to the suggestion that treatment with one or several GFs might promote oligodendroglial proliferation and remyelination.6-8

The therapeutic usefulness of GFs in MS will be determined in part by the location, duration and cellular composition of lesions in the patients selected for treatment. Bloodbrain barrier defects, inflammation, release of cytokines and activation of microglia are well-known features of MS lesions. These changes and their effects have been examined in tissue culture experiments9 in MS lesions and in animal models such as experimental autoimmune encephalomyelitis (EAE).10-15 The pathological processes that produce MS lesions are complex and overlap. Their occurrence and severity may vary in areas of the same lesion and in lesions that differ in age, size and location. Endothelial cells, oligodendrocytes, myelin sheaths, axons and astrocytes are targets in these pathological processes, and their responses probably have an important role in determining how much lesion repair and myelin regeneration occurs. Although much has been learned from studies of EAE, its variants and other MS models, species differences and other variables must be considered when evaluating their applicability to the development and repair of lesions in MS.