Ross Christina L, Siriwardane Mevan, Almeida-Porada Graça, Porada Christopher D, Brink Peter, Christ George J, Harrison Benjamin S
Wake Forest Institute for Regenerative Medicine, USA; Wake Forest Center for Integrative Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA.
Wake Forest Institute for Regenerative Medicine, USA.
Stem Cell Res. 2015 Jul;15(1):96-108. doi: 10.1016/j.scr.2015.04.009. Epub 2015 May 12.
Human bone marrow stromal cells (hBMSCs, also known as bone marrow-derived mesenchymal stem cells) are a population of progenitor cells that contain a subset of skeletal stem cells (hSSCs), able to recreate cartilage, bone, stroma that supports hematopoiesis and marrow adipocytes. As such, they have become an important resource in developing strategies for regenerative medicine and tissue engineering due to their self-renewal and differentiation capabilities. The differentiation of SSCs/BMSCs is dependent on exposure to biophysical and biochemical stimuli that favor early and rapid activation of the in vivo tissue repair process. Exposure to exogenous stimuli such as an electromagnetic field (EMF) can promote differentiation of SSCs/BMSCs via ion dynamics and small signaling molecules. The plasma membrane is often considered to be the main target for EMF signals and most results point to an effect on the rate of ion or ligand binding due to a receptor site acting as a modulator of signaling cascades. Ion fluxes are closely involved in differentiation control as stem cells move and grow in specific directions to form tissues and organs. EMF affects numerous biological functions such as gene expression, cell fate, and cell differentiation, but will only induce these effects within a certain range of low frequencies as well as low amplitudes. EMF has been reported to be effective in the enhancement of osteogenesis and chondrogenesis of hSSCs/BMSCs with no documented negative effects. Studies show specific EMF frequencies enhance hSSC/BMSC adherence, proliferation, differentiation, and viability, all of which play a key role in the use of hSSCs/BMSCs for tissue engineering. While many EMF studies report significant enhancement of the differentiation process, results differ depending on the experimental and environmental conditions. Here we review how specific EMF parameters (frequency, intensity, and time of exposure) significantly regulate hSSC/BMSC differentiation in vitro. We discuss optimal conditions and parameters for effective hSSC/BMSC differentiation using EMF treatment in an in vivo setting, and how these can be translated to clinical trials.
人骨髓基质细胞(hBMSCs,也称为骨髓来源的间充质干细胞)是一群祖细胞,其中包含骨骼干细胞(hSSCs)的一个亚群,能够再生软骨、骨骼、支持造血的基质和骨髓脂肪细胞。因此,由于其自我更新和分化能力,它们已成为再生医学和组织工程发展策略中的重要资源。SSCs/BMSCs的分化取决于暴露于有利于体内组织修复过程早期快速激活的生物物理和生化刺激。暴露于外源刺激如电磁场(EMF)可通过离子动力学和小信号分子促进SSCs/BMSCs的分化。质膜通常被认为是EMF信号的主要靶点,大多数结果表明由于受体位点作为信号级联的调节剂,对离子或配体结合速率有影响。离子通量与分化控制密切相关,因为干细胞沿特定方向移动和生长以形成组织和器官。EMF影响众多生物学功能,如基因表达、细胞命运和细胞分化,但仅在一定范围的低频以及低振幅内诱导这些效应。据报道,EMF可有效增强hSSCs/BMSCs的成骨和成软骨作用,且无不良影响的记录。研究表明特定的EMF频率可增强hSSC/BMSC的黏附、增殖、分化和活力,所有这些在将hSSCs/BMSCs用于组织工程中都起着关键作用。虽然许多EMF研究报告了分化过程的显著增强,但结果因实验和环境条件而异。在这里,我们综述了特定的EMF参数(频率、强度和暴露时间)如何在体外显著调节hSSC/BMSC的分化。我们讨论了在体内环境中使用EMF治疗有效诱导hSSC/BMSC分化的最佳条件和参数,以及如何将这些条件和参数转化为临床试验。
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