Huang Jianghong, Liang Yujie, Huang Zhiwang, Zhao Pengchao, Liang Qian, Liu Yonglong, Duan Li, Liu Wei, Zhu Feiyan, Bian Liming, Xia Jiang, Xiong Jianyi, Wang Daping
Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Shenzhen Kangning Hospital, Shenzhen Mental Health Center, Shenzhen, Guangdong Province, China.
ACS Biomater Sci Eng. 2019 May 13;5(5):2200-2207. doi: 10.1021/acsbiomaterials.9b00025. Epub 2019 Apr 5.
Pulsed electromagnetic field therapy, or pulsed signal therapy, has shown efficacy in treating many illnesses, including knee osteoarthritis. Although the mechanism is not fully understood, magnetic therapy is broadly welcomed because of its safe and noninvasive nature. At the cellular and molecular level, remote control of the cell fate by the magnetic field also has profound applications in both basic science and translational research. Here we demonstrate the use of pulsed electromagnetic field, one of the most benign and noninvasive extracellular cues, as a novel method to control specific chondrogenic differentiation of mesenchymal stem cells (MSCs). Chondrogenesis of transplanted MSCs inside the joint is considered one of the future therapies to rebuild the damaged cartilage. Here we show that pulsed electromagnetic field promotes chondrogenic differentiation of MSCs, and such a promoting effect can be drastically enhanced by the combined use of a magnetic hydrogel as the cell growth matrix. The magnetic hydrogel, synthesized by chemical cross-linking of gelatin and β-cyclodextrin and by embedding FeO magnetic nanoparticles in the hydrogel network, supports adhesion, growth, and proliferation of MSCs. Pulsed electromagnetic field boosts chondrogenesis of MSCs grown on the magnetic hydrogel, manifested by enhanced toluidine blue staining; higher expression of collagen II protein; and upregulation of collagen II, aggrecan, and SOX9 genes. Therefore, our work presents a robust method for chondrogenesis of MSCs using magnetic field as the external cue.
脉冲电磁场疗法，即脉冲信号疗法，已显示出对包括膝关节骨关节炎在内的多种疾病具有治疗效果。尽管其作用机制尚未完全明确，但磁疗因其安全无创的特性而广受青睐。在细胞和分子水平上，磁场对细胞命运的远程控制在基础科学和转化研究中也具有深远的应用价值。在此，我们展示了使用脉冲电磁场这一最为温和且无创的细胞外信号之一，作为一种控制间充质干细胞（MSCs）特定软骨生成分化的新方法。关节内移植的间充质干细胞软骨生成被认为是未来重建受损软骨的治疗方法之一。在此我们表明，脉冲电磁场可促进间充质干细胞的软骨生成分化，并且通过联合使用磁性水凝胶作为细胞生长基质，这种促进作用可显著增强。该磁性水凝胶由明胶和β - 环糊精化学交联，并将FeO磁性纳米颗粒嵌入水凝胶网络中合成，可支持间充质干细胞的黏附、生长和增殖。脉冲电磁场可促进在磁性水凝胶上生长的间充质干细胞的软骨生成，表现为甲苯胺蓝染色增强、胶原蛋白II蛋白表达升高以及胶原蛋白II、聚集蛋白聚糖和SOX9基因上调。因此，我们的工作提出了一种以磁场作为外部信号来促进间充质干细胞软骨生成的可靠方法。
