Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 124, Issue 1, Pages 54-65Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.13144FP
Keywords
neural stem cell; experimental autoimmune encephalomyelitis (EAE); osthole; anti-inflammation; remyelination
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Funding
- National Natural Science Foundation of China [81173580]
- Natural Science Foundation of Liaoning Province [201102144, 2013225086]
- Science Foundation of Shenyang City [F11-264-1-42]
- Liaoning Province Excellent Talents Project
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The therapeutic potential of adult neural stem cells (NSCs)-derived from bone marrow (BM) has been recently described in experimental autoimmune encephalomyelitis (EAR), an animal model of multiple sclerosis; however, the beneficial effects are modest due to their marginal anti-inflammatory capacity. To overcome this weakness and endow BM-NSC therapy with profound anti-inflammatory capacity, in this study we pretreated EAR mice with osthole, a natural coumarin with a broad spectrum of pharmacological activities, including anti-inflammation, immunomodulation, and neuroprotection, before NSC-application and continued throughout the study. We found that osthole conferred a potent anti-inflammatory capacity to this BM-NSC therapy, thus more profoundly suppressing ongoing EA and exhibiting significant advantages over conventional NSC-therapy as follows: 1) Enhanced anti-inflammatory effect, thus improving survival environment for engrafted BM-NSCs and protecting myelin sheaths from further demyelination; 2) Drove transplanted (exogenous) BM-NSCs to differentiate into more oligodendrocytes and neurons but inhibited differentiation into astrocytes, thus promoting remyelination and axonal growth, and reducing astrogliosis; and 3) augmented CNS neurotrophic support thus promoted resident (endogenous) repair of myelin/axonal damage. These effects make the BM-NSCs based therapy a more promising approach to enhance remyelination and neuronal repopulation, thus more effectively promoting anatomic and functional recovery from neurological deficits.
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