Osthole Augments Therapeutic Efficiency of Neural Stem Cells–Based Therapy in Experimental Autoimmune Encephalomyelitis

• Published in: Journal of Pharmacological Sciences 2014/01/20, Vol.124(1), pp.54-65
• Main Authors: Gao, Zhong, Wen, Qingping, Xia, Yang, Yang, Jingxian, Gao, Peng, Zhang, Nan, Li, Hongyan, Zou, Safeng
• Format: Article
• Language: English
• Subjects: Animals; anti-inflammation; Anti-Inflammatory Agents; Bone Marrow Transplantation; Cell Differentiation - drug effects; Cells, Cultured; Coumarins - pharmacology; Coumarins - therapeutic use; Demyelinating Diseases - prevention & control; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental - therapy; experimental autoimmune encephalomyelitis (EAE); Female; Graft Survival - drug effects; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Multiple Sclerosis - therapy; Myelin Sheath - pathology; neural stem cell; Neural Stem Cells - cytology; Neural Stem Cells - transplantation; Neurons; Neuroprotective Agents; Oligodendroglia; osthole; remyelination; Stem Cell Transplantation
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.13144FP

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.