Department of Surgery, National University of Singapore, Singapore, 119228, Singapore.
Biolonic Currents Electromagnetic Pulsing Systems Laboratory, BICEPS, National University of Singapore, Singapore, Singapore.
Stem Cell Res Ther. 2020 Feb 3;11(1):46. doi: 10.1186/s13287-020-1566-5.
The mesenchymal stem cell (MSC) secretome, via the combined actions of its plethora of biologically active factors, is capable of orchestrating the regenerative responses of numerous tissues by both eliciting and amplifying biological responses within recipient cells. MSCs are "environmentally responsive" to local micro-environmental cues and biophysical perturbations, influencing their differentiation as well as secretion of bioactive factors. We have previously shown that exposures of MSCs to pulsed electromagnetic fields (PEMFs) enhanced MSC chondrogenesis. Here, we investigate the influence of PEMF exposure over the paracrine activity of MSCs and its significance to cartilage regeneration.
Conditioned medium (CM) was generated from MSCs subjected to either 3D or 2D culturing platforms, with or without PEMF exposure. The paracrine effects of CM over chondrocytes and MSC chondrogenesis, migration and proliferation, as well as the inflammatory status and induced apoptosis in chondrocytes and MSCs was assessed.
We show that benefits of magnetic field stimulation over MSC-derived chondrogenesis can be partly ascribed to its ability to modulate the MSC secretome. MSCs cultured on either 2D or 3D platforms displayed distinct magnetic sensitivities, whereby MSCs grown in 2D or 3D platforms responded most favorably to PEMF exposure at 2 mT and 3 mT amplitudes, respectively. Ten minutes of PEMF exposure was sufficient to substantially augment the chondrogenic potential of MSC-derived CM generated from either platform. Furthermore, PEMF-induced CM was capable of enhancing the migration of chondrocytes and MSCs as well as mitigating cellular inflammation and apoptosis.
The findings reported here demonstrate that PEMF stimulation is capable of modulating the paracrine function of MSCs for the enhancement and re-establishment of cartilage regeneration in states of cellular stress. The PEMF-induced modulation of the MSC-derived paracrine function for directed biological responses in recipient cells or tissues has broad clinical and practical ramifications with high translational value across numerous clinical applications.
间充质干细胞（MSC）的分泌组，通过其众多生物活性因子的协同作用，能够通过在受体细胞内引发和放大生物反应，协调多种组织的再生反应。MSC 对局部微环境线索和生物物理干扰具有“环境响应”能力，影响其分化和生物活性因子的分泌。我们之前已经表明，将 MSC 暴露于脉冲电磁场（PEMF）中可增强 MSC 的软骨生成。在这里，我们研究了 PEMF 暴露对 MSC 旁分泌活性的影响及其对软骨再生的意义。
从接受或不接受 PEMF 暴露的 3D 或 2D 培养平台的 MSC 中生成条件培养基（CM）。评估 CM 对软骨细胞和 MSC 软骨生成、迁移和增殖的旁分泌作用，以及对软骨细胞和 MSC 的炎症状态和诱导凋亡的影响。
我们表明，磁场刺激对 MSC 衍生软骨生成的益处部分归因于其调节 MSC 分泌组的能力。在 2D 或 3D 平台上培养的 MSC 表现出不同的磁敏感性，其中在 2D 或 3D 平台上生长的 MSC 对 2mT 和 3mT 振幅的 PEMF 暴露反应最有利。10 分钟的 PEMF 暴露足以显著增强源自任一平台的 MSC 衍生 CM 的软骨生成潜力。此外，PEMF 诱导的 CM 能够增强软骨细胞和 MSC 的迁移，并减轻细胞炎症和凋亡。
这里报告的发现表明，PEMF 刺激能够调节 MSC 的旁分泌功能，以增强和重建细胞应激状态下的软骨再生。PEMF 诱导的 MSC 衍生旁分泌功能的调节，对于在受体细胞或组织中产生定向的生物学反应具有广泛的临床和实际意义，具有很高的跨众多临床应用的转化价值。
