脑出血（ICH）后星形胶质细胞（ASC）活化引起炎症反应是加重神经损伤的重要因素之一，并影响移植细胞的存活与分化。外胚间充质干细胞（EMSC）作为一种成体干细胞，用于移植治疗，取材方便、合乎伦理，可克服以往干细胞转化应用的瓶颈。最新研究表明EMSC还具有免疫调节作用，但具体机制尚不明确。本项目基于ICH后铁过载损伤机制的前期研究基础，结合EMSC和ASC通过Connexin43（Cx43）建立缝隙连接及ICH后Cx43表达下调的新发现，1）探讨Fe2+对ASC的激活作用及机制，2）验证EMSC与ASC通过Cx43建立缝隙连接从而调控Hippo通路抑制Fe2+介导的ASC活化，3）在ICH模型中探讨EMSC移植对血肿周围炎症微环境的改善、血脑屏障和残存神经元的保护作用以及神经功能改善情况。本研究将有助于阐明EMSC对ICH的免疫调节机制，促进EMSC移植的转化应用，为ICH的治疗提供新思路。

Neuroinflamation induced by astrocytes (ASC) activation after intracerebral hemorrhage (ICH) has been demonstrated as one of the mechanisms causing neurological deterioration. Inflammatory micro-environment can also inhibit the survival and differentiation of transplanted cells. As a novel adult stem cell, ecto-mesenchymal stem cell (EMSC) can be isolated from nasal mucosa, oral mucosa and dental pulp. It can be easily cultured in vitro. It helps to overcome the ethical bottleneck of translational research which limits clinical application of neural stem cells and mesenchymal stem cells in the past. Most recent research revealed the immunomodulation function of EMSC. Previously we have studied in detail the mechanisms of neural injury caused by iron overload after ICH. Recently we found Connexin43 (Cx43) was richly expressed in EMSC and ASC, Cx43 based gap junction can be built between these two cells. However, Cx43 was downregulated after ICH. Based on these findings, we come up with this proposal. We will explore the mechanism of ASC activation after ferrous chloride treatment. Then verify that EMSC can inhibit iron overload induced ASC activation by Cx43 based modulation of Hippo pathway. Furthermore, EMSC will be transplanted into ICH mice brain. Improvement of the inflammatory micro-environment, maintenance of blood brain barrier, protection of remaining neurons and amelioration of neurological deficit will be evaluated. This project is designed to clarify the immunomodulatory mechanism of EMSC on ICH induced ASC activation. It helps to promote transformation application of EMSC and provides immunomodulatory therapy strategy for ICH.