Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, California.
Department of Surgery, Stanford University, Palo Alto, California.
Stem Cells Transl Med. 2020 Aug;9(8):850-866. doi: 10.1002/sctm.19-0391. Epub 2020 Mar 10.
Mesenchymal stromal cells (MSCs) have been a popular platform for cell-based therapy in regenerative medicine due to their propensity to home to damaged tissue and act as a repository of regenerative molecules that can promote tissue repair and exert immunomodulatory effects. Accordingly, a great deal of research has gone into optimizing MSC homing and increasing their secretion of therapeutic molecules. A variety of methods have been used to these ends, but one emerging technique gaining significant interest is the use of ultrasound. Sound waves exert mechanical pressure on cells, activating mechano-transduction pathways and altering gene expression. Ultrasound has been applied both to cultured MSCs to modulate self-renewal and differentiation, and to tissues-of-interest to make them a more attractive target for MSC homing. Here, we review the various applications of ultrasound to MSC-based therapies, including low-intensity pulsed ultrasound, pulsed focused ultrasound, and extracorporeal shockwave therapy, as well as the use of adjunctive therapies such as microbubbles. At a molecular level, it seems that ultrasound transiently generates a local gradient of cytokines, growth factors, and adhesion molecules that facilitate MSC homing. However, the molecular mechanisms underlying these methods are far from fully elucidated and may differ depending on the ultrasound parameters. We thus put forth minimal criteria for ultrasound parameter reporting, in order to ensure reproducibility of studies in the field. A deeper understanding of these mechanisms will enhance our ability to optimize this promising therapy to assist MSC-based approaches in regenerative medicine.
间充质基质细胞（MSCs）由于其向损伤组织归巢的倾向以及作为促进组织修复和发挥免疫调节作用的再生分子储存库的作用，已成为再生医学中细胞治疗的热门平台。因此，大量的研究致力于优化 MSC 归巢和增加其治疗分子的分泌。已经使用了各种方法来实现这些目标，但一种新兴的技术正在引起人们的极大兴趣，即使用超声。声波对细胞施加机械压力，激活机械转导途径并改变基因表达。超声已应用于培养的 MSC 以调节自我更新和分化，以及感兴趣的组织以使其成为 MSC 归巢的更有吸引力的目标。在这里，我们回顾了超声在基于 MSC 的治疗中的各种应用，包括低强度脉冲超声、脉冲聚焦超声和体外冲击波治疗，以及辅助治疗如微泡的应用。在分子水平上，似乎超声会短暂地产生细胞因子、生长因子和粘附分子的局部梯度，从而促进 MSC 归巢。然而，这些方法的分子机制还远未完全阐明，并且可能因超声参数而异。因此，我们提出了超声参数报告的最低标准，以确保该领域研究的可重复性。更深入地了解这些机制将增强我们优化这种有前途的治疗方法的能力，以帮助基于 MSC 的方法在再生医学中发挥作用。
