Iron Oxide Nanoparticle-Mediated Development of Cellular Gap Junction Crosstalk to Improve Mesenchymal Stem Cells' Therapeutic Efficacy for Myocardial Infarction
Iron Oxide Nanoparticle-Mediated Development of Cellular Gap Junction Crosstalk to Improve Mesenchymal Stem Cells' Therapeutic Efficacy for Myocardial Infarction
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DOI：
10.1021/nn506732n
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发表时间：
2015-03-01
期刊：
影响因子：
17.1
通讯作者：
Kim, Byung-Soo
中科院分区：
文献类型：
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作者：
Han, Jin;Kim, Bokyoung;Kim, Byung-Soo
间充质干细胞(MSCs)的电生理表型发育和旁分泌作用是决定MSCs治疗心肌梗死疗效的关键因素。在这方面，MSCs与心肌细胞的共培养为MSCs的心脏启动提供了一个平台。尤其是在共培养过程中，MSCs与心肌细胞的主动缝隙连接串扰在MSC的共培养修饰中起着重要作用。在此，我们报道了氧化铁纳米颗粒(IONPs)显著增强了心肌母细胞(H9C2)缝隙连接蛋白43(Cx43)的表达，这对于与MSCs共培养产生治疗潜力增强的MSCs的缝隙连接通讯至关重要。与携带IONP的H9C2共培养的MSCs(共培养的MSCs：cMSCs)表现出与H9C2活跃的细胞串扰，并显示出显著更高的心脏电生理生物标志物水平和有利于心脏修复的旁分泌特征，两者都负责心肌梗死的修复。因此，与注射未经修饰的MSCs相比，将cMSC注射到大鼠MI模型中可显著改善动物存活率和心功能。本研究强调了IONPs在发展细胞间缝隙连接串扰和产生超过传统MSCs修复潜力的cMSCs方面的应用。基于我们的发现，IONPs在细胞生物学和干细胞治疗方面的潜在应用可以被扩展。
Electrophysiological phenotype development and paracrine action of mesenchymal stem cells (MSCs) are the critical factors that determine the therapeutic efficacy of MSCs for myocardial infarction (MI). In such respect, coculture of MSCs with cardiac cells has windowed a platform for cardiac priming of MSCs. Particularly, active gap junctional crosstalk of MSCs with cardiac cells in coculture has been known to play a major role in the MSC modification through coculture. Here, we report that iron oxide nanoparticles (IONPs) significantly augment the expression of connexin 43 (Cx43), a gap junction protein, of cardiomyoblasts (H9C2), which would be critical for gap junctional communication with MSCs in coculture for the generation of therapeutic potential-improved MSCs. MSCs cocultured with IONP-harboring H9C2 (cocultured MSCs: cMSCs) showed active cellular crosstalk with H9C2 and displayed significantly higher levels of electrophysiological cardiac bionnarkers and a cardiac repair-favorable paracrine profile, both of which are responsible for MI repair. Accordingly, significantly improved animal survival and heart function were observed upon cMSC injection into rat MI models compared with the injection of unmodified MSCs. The present study highlights an application of IONPs in developing gap junctional crosstalk among the cells and generating cMSCs that exceeds the reparative potentials of conventional MSCs. On the basis of our finding, the potential application of IONPs can be extended in cell biology and stem cell-based therapies.