Affiliations: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul, Korea | Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, MI, USA | Department of Chemistry, College of Advanced Science, Dankook University, Cheonan, Korea | Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA | Department of Orthopedic Surgery, Korea University Anam Hospital, Seoul, Korea
Note: [] Address for correspondence: Dr. Sang-Hoon Lee, Department of Biomedical Engineering, College of Health Science, Korea University, Jeongneung-dong, Seongbuk-gu, Seoul 136-703, Korea. Tel.: +82 2 940 2881; Fax: +82 2 921 6818; E-mail: [email protected].
Abstract: Slow interstitial flow can lead to large changes in cell morphology. Since conventional biological assays are adapted to two-dimensional culture protocols, there is a need to develop a microfluidic system that can generate physiological levels of interstitial flow. Here we developed a system that uses a passive osmotic pumping mechanism to generate sustained and steady interstitial flows for two-dimensional cultures. Two different cell types, fibroblasts and mesenchymal stem cells, were selected because they are generally exposed to interstitial flow. To quantify the cellular response to interstitial shear flow in terms of proliferation and alignment, 4 rates of flow were applied. We found that the proliferation rate of fibroblasts varied linearly with wall shear stress. In addition, alignment of fibroblast cells depended linearly on the magnitude of the shear stress, whereas mesenchymal stem cells were aligned regardless of the magnitude of shear stress. This suggested that mesenchymal stem cells are very sensitive to shear stresses, even at levels generated by interstitial flow. The results presented here emphasize the need to consider the mechanosensitivity and the natural role of different cell types when evaluating their responses to fluid flow.
