星形胶质细胞（ASC）作为脑内主要支持细胞，在脑出血后发生氧化应激和凋亡，是加重神经损伤、影响细胞移植治疗效果的主要因素。本项目基于前期发现鼻粘膜外胚间充质干细胞（eMSC）与ASC形成缝隙连接，且Connexin43（Cx43）介导的细胞间通讯连接参与脑出血后移植细胞和宿主细胞间的相互调控和神经保护，然而其可能参与介导的外源性线粒体转移机制有待进一步研究。本课题拟利用Cx43-siRNA，突变型Cx43载体，及条件性Cx43敲除小鼠等手段，分别阐述eMSC来源线粒体转移对ASC保护作用受到Cx43调控及其相关机制：1）Cx43介导eMSC产生含有线粒体的细胞外微泡；2）eMSC来源的线粒体转移过程对血红素诱导的ASC氧化应激和凋亡的影响；3）eMSC移植对脑出血后小鼠血肿周围ASC抗氧化、抗凋亡作用以及神经功能的改善作用。本研究将有助于促进eMSC移植的转化应用，为干细胞治疗提供新思路。

As major supporting cells in the brain, astrocytes (ASC) experience oxidative stress and apoptosis after intracerebral hemorrhage. They play a critical role in the deterioration of the brain injury and the attenuation of the therapeutic benefit of cell transplantation. Our previous findings indicate that ecto-mesenchymal stem cells (eMSC) and ASC can form gap junctions, and that intercellular communication mediating by Cx43 is involved in the mutual regulation between transplant cells and host cells, as well as in the neuroprotection. Nevertheless, the specific role of Cx43 in its possibly mediating exogenous mitochondrial transfer is still unclear. Based on these observations, this project is planning to use different methods such as Cx43-siRNA, mutant Cx43 vector and conditional Cx43 knockout mice to manifest the ASC protecting of eMSC derived mitochondrial transfer which is regulated by Cx43 and its related mechanisms; including: 1) Cx43 mediates eMSC to product extracellular microvesicles containing mitochondria; 2) The eMSC-derived mitochondrial transfer influences hemin-induced oxidative stress and apoptosis of ASC ; 3) The eMSC transplantation on post-hemorrhage stage mice exerts anti-oxidation and anti-apoptotic effects on perihematomal ASC and brings improvement of neurological function. This study will accelerate the translational application of eMSC transplantation and provide new ideas for stem cell therapy.