A Microfluidic Platform for Investigating Transmembrane Pressure-Induced Glomerular Leakage
Ting-Hsuan Chen,
Jie-Sheng Chen,
Yi-Ching Ko,
Jyun-Wei Chen,
Hsueh-Yao Chu,
Chih-Shuan Lu,
Chiao-Wen Chu,
Hsiang-Hao Hsu,
Fan-Gang Tseng
Affiliations
Ting-Hsuan Chen
Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Hong Kong, China
Jie-Sheng Chen
Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan
Yi-Ching Ko
Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan 33305, Taiwan
Jyun-Wei Chen
Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan
Hsueh-Yao Chu
Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan
Chih-Shuan Lu
Institute of Nano Engineering and Microsystems, National Tsing Hua University, Hsinchu 30013, Taiwan
Chiao-Wen Chu
Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan
Hsiang-Hao Hsu
Department of Nephrology, Kidney Research Center, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan 33305, Taiwan
Fan-Gang Tseng
Department of Engineering and System Science, Frontier Research Center on Fundamental and Applied Sciences of Matters, National Tsing Hua University, Hsinchu 30013, Taiwan
Transmembrane pressure across the glomerular filter barrier may underlie renal failure. However, studies of renal failure have been difficult owing to a lack of in vitro models to capture the transmembrane pressure in a controlled approach. Here we report a microfluidic platform of podocyte culture to investigate transmembrane pressure induced glomerular leakage. Podocytes, the glomerular epithelial cells essential for filtration function, were cultivated on a porous membrane supplied with transmembrane pressure ΔP. An anodic aluminum oxide membrane with collagen coating was used as the porous membrane, and the filtration function was evaluated using dextrans of different sizes. The results show that dextran in 20 kDa and 70 kDa can penetrate the podocyte membrane, whereas dextran in 500 kDa was blocked until ΔP ≥ 60 mmHg, which resembles the filtration function when ΔP was in the range of a healthy kidney (ΔP < 60 mmHg) as well as the hypertension-induced glomerular leakage (ΔP ≥ 60 mmHg). Additionally, analysis showed that synaptopodin and actin were also downregulated when ΔP > 30 mmHg, indicating that the dysfunction of renal filtration is correlated with the reduction of synaptopodin expression and disorganized actin cytoskeleton. Taking together, our microfluidic platform enables the investigation of transmembrane pressure in glomerular filter membrane, with potential implications for drug development in the future.
