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 myelinate normally. However, a progressive CNS demyelination begins at 3-4 months 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 the adult CNS. Either CG4 cells, or co-grafts of CG4/B 104 cells 11:1 ratio respectively) were performed. Grafted cells survived and migrated in the normal and transgenic brain. Non-treated transgenic animals revealed extensive lack of myelin. Three months post-transplant hosts with CG4 or co-transplants displayed a near normal myelin pattern. Double immunofluorescence for neurofilament and myelin basic protein revealed the presence of many naked axons in non-grafted transgenic animals. Those grafted with progenitor CG4 cells or cografts displayed a clear increase in remyelination. This data provides a new direction for the development of cell replacement therapies in demyelinating diseases.
Espinosa de los Monteros
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A
Mental Retardation Research Center, Neuropsychiatric Institute, Departments of Neurobiology and Psychiatry, UCLA School of Medicine, Los Angeles, CA, USA. aespinosa@mednet.ucla.edu
Baba
H
H
Zhao
P M
PM
Pan
T
T
Chang
R
R
de Vellis
J
J
Ikenaka
K
K
D000818:Animals; D001927:Brain Diseases / Q000503:physiopathology* / Q000601:surgery*; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D003711:Demyelinating Diseases / Q000503:physiopathology* / Q000601:surgery*; D019085:Fluorescent Antibody Technique, Direct / Q000379:methods; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology; D009836:Oligodendroglia / Q000502:physiology / Q000637:transplantation*; D012333:RNA, Messenger / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D014168:Transferrin / Q000235:genetics
D004676:Myelin Basic Protein; D012333:RNA, Messenger; D014168:Transferrin