Structural And Functional Remodeling Of The Insulted Brain After Transplantation Of Neural Stem-like Cells Derived From Bone Marrow Mesenchymal Stem Cells Into The Rats With Severe Acute Carbon Monoxide Poisoning

Objective:We investigated the feasibility and efficacy of bone marrow mesenchymal stem cells(BMSCs)-derived neural stem-like cells(MS-NSCs) therapy on delayed neurologic sequelae(DNS)in rats after severe acute carbon monoxide poisoning.Design:Prospective,randomized,controlled trial.Setting:A research laboratory of a university hospital.Subjects:Sprague-Dawley rats weighing 230±20 g and 90±10 gInterventions:The rats were exposed to a mixture of 1,000 ppm CO in air for 40 mins,then 3,000 ppm for another 20 mins until they lost consciousness. Approximately 7×10~6 allogeneic BMSCs or MS-NSCs labelled with BrdU were infused into the poisoned rats via the left internal carotid after 24 hours resuscitation respectively.The poisoned rats for control were treated with equivalent phosphate buffered saline.Measurements and Main Results:The neurologic and cognitive functions were evaluated by Neurological Severity Scores and Morris Water Maze(MWM)tests, while the changes of cerebral structure were assessed by immunohistochemistry assay,myelin and hematoxylin- eosin staining at 5 weeks after cellular therapy. The findings demonstrated that the cellular transplantation could improve the compactness and regulation of the structure arrangement within the insulted white matter.Transplanted MS-NSCs colonizing in hippocampus were positive for MAP2(84.6±5.6%)and for GFAP in subventricular white matter and hippocampus(32.2±2.5%;9.7±1.2%),meanwhile the fraction was larger than BMSCs expression of the above markers in corresponding domains. Furthermore,MS-NSCs showed comparatively a higher survival rate in the most domains of the diffusively injured brain,which maybe had contributed to the better improvement in the MWM test(p＜0.05).Conclusions:The stem cell-based therapy is probably another effective approach to DNS after severe acute CO poisoning;moreover,MS-NSCs induced in vitro preliminarily is potentially more efficient than direct handling of nontreated BMSCs.