Remyelination of the adult demyelinated mouse brain by grafted oligodendrocyte progenitors and the effect of B-104 cografts

The 4e transgenic mouse is characterized by overexpression of the PLP gene. Heterozygous littermates containing three PLP gene copies develop and myel inate normally. However, a progressive CNS demyelination begins at 3-4 mont hs of age. Despite focal demyelination, these animals survive for one year with hind limb paralysis. We used this CNS demyelination model to determine if grafts of CG4 oligodendrocyte progenitors would survive and myelinate t he adult CNS. Either CG4 cells, or co-grafts of CG4/B104 cells 11:1 ratio r espectively) were performed. Grafted cells survived and migrated in the nor mal and transgenic brain. Non-treated transgenic animals revealed extensive lack of myelin, Three months post-transplant hosts with CG4 or co-transpla nts displayed a near normal myelin pattern. Double immunofluorescence for n eurofilament and myelin basic protein revealed the presence of many naked a xons in nongrafted transgenic animals. Those grafted with progenitor CG4 ce lls or cografts displayed a clear increase in remyelination. This data prov ides a new direction for the development of cell replacement therapies in d emyelinating diseases.