Department of Medical Imaging, Taipei Tzuchi Hospital, Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan.
Institute of Biomedical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Int J Nanomedicine. 2020 Nov 19;15:9181-9195. doi: 10.2147/IJN.S278687. eCollection 2020.
Stem cell therapy for ischemic stroke has shown success in experimental settings, but its translation into clinical practice is challenging. The choroid plexus (CP) plays a regulatory role in neural regeneration. Mesenchymal stem cells (MSCs) promote neurogenesis in the ventricular-subventricular zone. However, it is unclear whether MSCs interact with the CP in brain tissue repair.
Rat (r)MSCs were labeled with iron oxide nanoparticles (IONs) and transduced with red fluorescent protein, and then injected into the brain of rats with ischemic stroke and monitored over time by magnetic resonance imaging. The functional recovery of rats was determined by the corner test score, Modified Neurological Severity score, and stroke volume. MSCs and CP were also co-cultured for 14 days, and the medium was analyzed with a cytokine array.
In vivo imaging and histologic analysis revealed that ION-labeled MSCs were mainly located at the injection site and migrated to the infarct area and to the CP. Functional recovery was greater in rats treated with MSCs as compared to those that received mock treatment. Bidirectional enhancement of proliferation in MSCs and CP was observed in the co-culture; moreover, MSCs migrated to the CP. Cytokine analysis revealed elevated levels of proliferation- and adhesion-related cytokines and chemokines in the culture medium. Wikipathway predictions indicated that insulin-like growth factor 1/Akt signaling (WP3675), chemokine signaling pathway (WP2292), and spinal cord injury (WP2432) are involved in the increased proliferation and migration of MSCs co-cultured with the CP.
Crosstalk with the CP enhances MSC proliferation and migration in a transwell assay. Moreover, MRI reveals MSC migration towards the CP in an ischemic stroke model. The secreted factors resulting from this interaction have therapeutic potential for promoting functional recovery in the brain after ischemic stroke.
干细胞疗法治疗缺血性中风在实验环境中已取得成功，但将其转化为临床实践具有挑战性。脉络丛（CP）在神经再生中起调节作用。间充质干细胞（MSCs）促进脑室-室下区的神经发生。然而，MSCs 是否与脑组织修复中的 CP 相互作用尚不清楚。
用氧化铁纳米颗粒（IONs）标记大鼠（r）MSCs，并转导红色荧光蛋白，然后将其注射到缺血性中风大鼠的大脑中，并通过磁共振成像随时间进行监测。通过转角试验评分、改良神经损伤评分和中风体积来确定大鼠的功能恢复情况。还将 MSCs 和 CP 共培养 14 天，并通过细胞因子阵列分析培养基。
体内成像和组织学分析显示，ION 标记的 MSCs 主要位于注射部位，并迁移到梗塞区和 CP。与接受模拟治疗的大鼠相比，接受 MSCs 治疗的大鼠的功能恢复更好。共培养中观察到 MSCs 和 CP 的增殖呈双向增强；此外，MSCs 迁移到 CP。细胞因子分析显示，培养物中增殖和黏附相关细胞因子和趋化因子的水平升高。Wikipathway 预测表明，胰岛素样生长因子 1/Akt 信号通路（WP3675）、趋化因子信号通路（WP2292）和脊髓损伤（WP2432）参与了 CP 共培养中 MSC 增殖和迁移的增加。
与 CP 的相互作用增强了 MSC 在 Transwell 测定中的增殖和迁移。此外，MRI 显示 MSC 在缺血性中风模型中向 CP 迁移。这种相互作用产生的分泌因子具有促进缺血性中风后大脑功能恢复的治疗潜力。
