Co-transplantation of bone mesenchymal stem cells combined with janus kinase-signal transducer and activators of transcription 3 signaling pathway inhibitor (AG490) for focal cerebral ischemia/reperfusion injury in rats

Abstract

Objective To investigate the neuroprotective effect of combined application of rat bone mesenchymal stem cells （BMSCs） and janus kinase-signal transducer and activators of transcription 3 （JAK- STAT） signaling pathway inhibitor （AG490） on rat focal cerebral ischemia. Methods In all rats, the mid- dle cerebral artery occlusion （MCAO） was produced by occlusion of right internal carotid artery with a nylon monofilament. 100 male Spragne-Dawley （SD） rats were divided into four groups according to random digits table （n = 20 in each group）, including sham group, 1% DMSO transplanted group, AG490 transplanted group, BMSCs ± 1% DMSO transplanted group and BMSCs ± AG490 transplanted group. The phosphorylated signal transducer and activator of transcription3 （STAT3） （Tyr705） protein was measured by using Western blotting 24 h after transplantation. Cell apoptosis was examined by TdT-mediated dUTP nick end labeling （TUNEL）. The neurological defective scores were assessed at 3rd, 7th, and 14th day after reperfusion re- spectively in each experiment and all the animals were then decapitated to determine the brain infarct vol- ume and brain water content. Results The expression of phosphorylated （Tyr705） STAT3 was decreased significantly after right intracerebral ventricle injection. Co-transplantation of bone mesenchymal stem cells and AG490 could significantly decrease the number of apoptotic cells and infarct volume [ （12. 31 ± 6. 24）% ], brain water content in ischemia hemisphere [ （77.55 ± 0. 53 ）% ]. The neurological defective scores in BMSCs ± AG490 transplanted group （ 1.63 ± 0. 35 ） were lower than other transplanted groups （P 〈 0.05 ）. Conclusion Co-transplantation of bone mesenchymal stem cells and AG490 produces a synergistic neuroprotective effect. Key words: Cerebral ischemia; Reperfusion injury; Janus kinase-signal transducer and acti-vators of transcription 3 signaling pathway; Bone mesenchymal stem cell transplantation