Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Department of Emergency, Affiliated Hospital of Guizhou Medical University, Guiyang, People's Republic of China.
J Cell Biochem. 2019 Sep;120(9):14372-14382. doi: 10.1002/jcb.28693. Epub 2019 Apr 8.
Adipose-derived mesenchymal stromal cells (ADSCs) exhibited high potential in tissue repair and regeneration, and it has been proved that ADSCs could protect brain cells from apoptosis and maintaining blood-brain barrier stability after cerebral vascular disease. In this study, we evaluated the therapeutic potential and mechanism of ADSCs stereotactic transplantation in intracerebral hemorrhage (ICH) mice model and hemin-treated astrocytes. Mice were divided into three groups: sham group, ICH + PBS group, and ICH + ADSC group. Mice in ICH + ADSC group received ADSCs cell suspension stereotactic transplantation into the area beside the bleeding region. Astrocytes were divided into three groups: control group, hemin group, and hemin + ADSC group. Astrocytes in hemin + ADSC group were cultured in ADSCs-astrocyte no-contact coculture system and treated with 30 μM hemin solution. The results showed that ADSCs stereotactic transplantation improved functional outcomes and reduced cell apoptosis after ICH. Moreover, ADSCs stereotactic transplantation could alleviate brain edema and inflammation and AQP4 protein expression contributed to the alleviation of brain edema. In addition, mitogen-activated protein kinase (MAPK) pathways, including p38/MAPK pathway and c-Jun N-terminal kinase pathway, were involved in AQP4 modulation by ADSCs transplantation in ICH. In conclusion, ADSCs transplantation could alleviate the nervous tissue injury, reduce cell apoptosis, and relieve brain edema in ICH. And the edema regulation effect of ADSCs transplantation is associated with inhibition of inflammation and AQP4 protein expression.
脂肪间充质基质细胞（ADSCs）在组织修复和再生方面表现出巨大潜力，已有研究证明 ADSCs 可保护脑细胞免于细胞凋亡，并在脑血管疾病后维持血脑屏障的稳定性。在本研究中，我们评估了 ADSCs 立体定向移植在脑出血（ICH）小鼠模型和血红素处理星形胶质细胞中的治疗潜力及其机制。小鼠被分为三组：假手术组、ICH+PBS 组和 ICH+ADSC 组。ICH+ADSC 组小鼠接受 ADCS 细胞悬液立体定向移植到出血区域旁的区域。星形胶质细胞分为三组：对照组、血红素组和血红素+ADSC 组。血红素+ADSC 组的星形胶质细胞在 ADSC-星形胶质细胞无接触共培养系统中培养，并接受 30μM 血红素溶液处理。结果表明，ADSCs 立体定向移植可改善 ICH 后功能结局和减少细胞凋亡。此外，ADSCs 立体定向移植可减轻脑水肿和炎症，AQP4 蛋白表达的减少有助于脑水肿的缓解。此外，丝裂原活化蛋白激酶（MAPK）通路，包括 p38/MAPK 通路和 c-Jun N-末端激酶通路，参与了 ADSCs 移植对 ICH 中 AQP4 的调节。总之，ADSCs 移植可减轻脑出血引起的神经组织损伤，减少细胞凋亡，减轻脑水肿。ADSCs 移植的水肿调节作用与抑制炎症和 AQP4 蛋白表达有关。
