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.
Department of Interventional Therapy, Department of Rehabilitation, Dalian Municipal Central Hospital, China.
Zhong
Z
Gao
Qingping
Q
Wen
Yang
Y
Xia
Jingxian
J
Yang
Peng
P
Gao
Nan
N
Zhang
Hongyan
H
Li
Safeng
S
Zou
D000818:Animals; D000893:Anti-Inflammatory Agents; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology* / Q000627:therapeutic use*; D003711:Demyelinating Diseases / Q000517:prevention & control; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000628:therapy*; D009186:Myelin Sheath / Q000473:pathology; D058953:Neural Stem Cells / Q000166:cytology / Q000637:transplantation*; D009474:Neurons; D018696:Neuroprotective Agents; D009836:Oligodendroglia; D033581:Stem Cell Transplantation
D000893:Anti-Inflammatory Agents; D003374:Coumarins; D018696:Neuroprotective Agents; C046627:osthol