Combination Therapy With Fingolimod and Neural Stem Cells Promotes Functional Myelination in vivo Through a Non-immunomodulatory Mechanism

Frontiers in Cellular Neuroscience
Yuan ZhangGuang-Xian Zhang

Abstract

Myelination, which occurs predominantly postnatally and continues throughout life, is important for proper neurologic function of the mammalian central nervous system (CNS). We have previously demonstrated that the combination therapy of fingolimod (FTY720) and transplanted neural stem cells (NSCs) had a significantly enhanced therapeutic effect on the chronic stage of experimental autoimmune encephalomyelitis, an animal model of CNS autoimmunity, compared to using either one of them alone. However, reduced disease severity may be secondary to the immunomodulatory effects of FTY720 and NSCs, while whether this therapy directly affects myelinogenesis remains unknown. To investigate this important question, we used three myelination models under minimal or non-inflammatory microenvironments. Our results showed that FTY720 drives NSCs to differentiate into oligodendrocytes and promotes myelination in an ex vivo brain slice culture model, and in the developing CNS of healthy postnatal mice in vivo. Elevated levels of neurotrophic factors, e.g., brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, were observed in the CNS of the treated infant mice. Further, FTY720 and NSCs efficiently prolonged the sur...Continue Reading

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Citations

Jun 25, 2019·Frontiers in Cellular Neuroscience·Yuan ZhangXing Li
Aug 28, 2020·Brain Research Bulletin·Li Zhang, Handong Wang

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Methods Mentioned

BETA
dissection
PCR
Profiler
confocal microscopy
light microscopy

Software Mentioned

ImageJ
Pro
Image
ImagePro
GraphPad Prism
Pro Plus

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