缺血性中风（IS）是一种严重且可能危及生命的疾病，治疗选择有限，通常会导致严重残疾。骨髓基质细胞（BMSC）移植在脑缺血再灌注损伤（CIRI）后表现出有希望的神经保护作用。然而，通过静脉给药时，其归巢率较低，从而阻碍了其有效性。在本研究中，我们旨在通过慢病毒转染表达岩藻糖基转移酶7来增强BMSCs的归巢能力。这种糖基化改造BMSCs上的CD44以表达造血细胞E-选择素/L-选择素配体（HCELL），这是最有效的E-选择素配体（HCELL）。选择素配体。强制 HCELL 表达后，在大脑中动脉闭塞 (MCAO) 模型中评估 BMSC 的移植。结果显示，HCELL BMSC 显着改善神经功能缺损并减少脑梗塞体积。此外，移植通过上调 BCL-2 和下调 BAX 导致细胞凋亡减少，还降低了炎症因子的 mRNA 水平，如白介素-1β (IL-1β)、IL-2、IL-6以及缺血脑组织中的肿瘤坏死因子-α（TNF-α）。值得注意的是，强化的 HCELL 表达促进了 BMSC 向脑缺血病变的迁移，并通过上调 PTGS-2、增加 PGE2 的产生和激活 VLA-4 来促进其随后的跨内皮迁移。总之，我们的研究表明，HCELL BMSC 移植可有效缓解 CIRI，并且强制 HCELL 表达可增强 BMSC 向脑缺血病变的归巢及其通过 PTGS-2/PGE2/VLA-4 的跨内皮迁移。这些发现表明 HCELL 在 BMSC 上的强制表达可以作为治疗缺血性中风的一种有前景的治疗策略。© 作者 2024。由牛津大学出版社出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Ischemic stroke (IS) is a significant and potentially life-threatening disease with limited treatment options, often resulting in severe disability. Bone marrow stromal cells (BMSCs) transplantation has exhibited promising neuroprotection following cerebral ischemia-reperfusion injury (CIRI). However, the effectiveness is hindered by their low homing rate when administered through the vein. In this study, we aimed to enhance the homing ability of BMSCs through lentivirus transfection to express fucosyltransferase 7. This glycosylation engineered CD44 on BMSCs to express hematopoietic cell E-selectin/L-selectin ligand (HCELL), which is the most potent E-selectin ligand. Following enforced HCELL expression, the transplantation of BMSCs was then evaluated in a middle cerebral artery occlusion (MCAO) model. Results showed that HCELL+BMSCs significantly ameliorated neurological deficits and reduced the volume of cerebral infarction. Furthermore, the transplantation led to a decrease in apoptosis by up-regulating BCL-2 and down-regulating BAX, also reduced the mRNA levels of inflammatory factors, such as interleukin-1β (IL-1β), IL-2, IL-6 and tumor necrosis factor-alpha (TNF-α) in the ischemic brain tissue. Notably, enforced HCELL expression facilitated the migration of BMSCs towards cerebral ischemic lesions and their subsequent transendothelial migration through the up-regulation of PTGS-2, increased production of PGE2 and activation of VLA-4. In summary, our study demonstrates that transplantation of HCELL+BMSCs effectively alleviates CIRI, and that enforced HCELL expression enhances the homing of BMSCs to cerebral ischemic lesions and their transendothelial migration via PTGS-2/PGE2/VLA-4. These findings indicate that enforced expression of HCELL on BMSCs could serve as a promising therapeutic strategy for the treatment of ischemic stroke.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.