Lee Eun-Joong, Hwang Chang-Mo, Baek Dong-Hyun, Lee Sang-Hoon
Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, Republic of Korea.
Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:6034-7. doi: 10.1109/IEMBS.2009.5333169.
Cell migration and proliferation are major process in wound healing, cancer metastasis and organogenesis during development. Many cells are related to recovery process of wound. Especially, fibroblasts act an important role in wound healing. Various cytokines such as platelet derived growth factor (PDGF) can induce fibroblast migration and widely studied to investigate the cell response under controlled cytokine microenvironments during wound healing. In real tissue healing process, cell microenvironments change with tissue types and anatomical characteristics of organs. With microfluidic system, we tried to mimic the natural microenvironment of wound healing, with gradient of PDGF, a fibroblast migration inducing cytokine, and patterned substrate with different orientation to PDGF gradient. Fibroblasts cultured in PDGF gradient micro fluidic chip showed cell migration under various micro environmental gradient conditions. Cells were cultured under PDGF gradient condition and different substrate pattern. Mouse fibroblast L929 cells were cultured in the microfluidic gradient. The results showed that most cells migrated along the substrate topological patterns under high concentration of PDGF. We developed long range sustaining micro fluidic channel and could analyze cell migration along the gradient of PDGF. Also, the cell migration on patterned extracellular environment shows that cells migrate along the extracellular 3D pattern rather than directly along the cytokine gradient when the pattern height is less than 1 microm. In this study, we could demonstrate that the extracellular pattern is more dominant to cell migration in combination with cytokine gradient in the wounded tissue when the environmental cues are 20 microm.
细胞迁移和增殖是伤口愈合、癌症转移以及发育过程中器官形成的主要过程。许多细胞都与伤口的恢复过程相关。尤其是成纤维细胞在伤口愈合中发挥着重要作用。多种细胞因子，如血小板衍生生长因子（PDGF），可诱导成纤维细胞迁移，并且人们对其进行了广泛研究，以探究伤口愈合过程中在可控细胞因子微环境下的细胞反应。在实际的组织愈合过程中，细胞微环境会随着组织类型和器官的解剖学特征而变化。利用微流控系统，我们试图模拟伤口愈合的自然微环境，设置PDGF（一种诱导成纤维细胞迁移的细胞因子）梯度以及具有不同PDGF梯度取向的图案化基质。在PDGF梯度微流控芯片中培养的成纤维细胞在各种微环境梯度条件下均表现出细胞迁移。细胞在PDGF梯度条件和不同的基质图案下进行培养。小鼠成纤维细胞L929在微流控梯度中培养。结果表明，在高浓度PDGF条件下，大多数细胞沿着基质拓扑图案迁移。我们开发了长距离维持微流控通道，并能够分析细胞沿PDGF梯度的迁移情况。此外，在图案化细胞外环境中的细胞迁移表明，当图案高度小于1微米时，细胞沿着细胞外三维图案迁移，而不是直接沿着细胞因子梯度迁移。在本研究中，我们能够证明，当环境线索为20微米时，在受伤组织中，细胞外图案与细胞因子梯度相结合对细胞迁移的影响更为显著。
