Osthole augments therapeutic efficiency of neural stem cells-based therapy in experimental autoimmune encephalomyelitis

The therapeutic potential of adult neural stem cells (nscs)-derived from bone marrow (bm) has been recently described in experimental autoimmune encephalomyelitis (eae),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 eae 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. © the japanese pharmacological society.