Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan.
J Orthop Res. 2013 Feb;31(2):322-7. doi: 10.1002/jor.22215. Epub 2012 Aug 21.
Guided cell migration is important in tissue development, repair, and engineering. We have previously demonstrated that applied electric fields (EFs) enhanced and directed ligament fibroblast migration and collagen production, depending on EF parameters. Electrical stimulation is widely used for the treatment of pain and to promote wound healing. In orthopaedic practices, applied EFs promote bone healing and ligament repair in vivo. In the current study, stimulation waveforms used in physical therapy for promoting tissue repair were adapted to examine their effects on ACL fibroblast migration. Using different waveform and field strengths, we discovered a decoupling of cell motility and directionality, which suggests disparate mechanisms. Integrin, a major extracellular matrix receptor, polarized in response to applied EFs and controlled cell directionality and signaling. Furthermore, we demonstrated that RhoA is a mediator between integrin aggregation and directed cell migration. Polarization is essential in directed cell migration and our study establishes an outside-in signaling mechanism for EF-induced cell directionality.
引导细胞迁移在组织发育、修复和工程中很重要。我们之前已经证明，应用电场（EF）可以增强和指导韧带成纤维细胞的迁移和胶原产生，具体取决于 EF 参数。电刺激广泛用于治疗疼痛和促进伤口愈合。在矫形实践中，应用 EF 可促进体内骨愈合和韧带修复。在当前的研究中，适应物理治疗中用于促进组织修复的刺激波形来检查它们对 ACL 成纤维细胞迁移的影响。使用不同的波形和场强，我们发现细胞迁移和方向性的解耦，这表明存在不同的机制。整合素是主要的细胞外基质受体，对外界施加的 EF 有极化反应，控制细胞的方向性和信号转导。此外，我们证明 RhoA 是整合素聚集和定向细胞迁移之间的介质。极化对于定向细胞迁移至关重要，我们的研究建立了 EF 诱导细胞定向的外向内信号机制。
