title: Lab on a chip-based hepatic sinusoidal system simulator for optimal primary hepatocyte culture.
abstract: Primary hepatocyte cultures have been used in studies on liver disease, physiology, and pharmacology. While they are an important tool for in vitro liver studies, maintaining liver-specific characteristics of hepatocytes in vitro is difficult, as these cells rapidly lose their unique characteristics and functions. Portal flow is an important condition to preserve primary hepatocyte functions and liver regeneration in vivo. We have developed a microfluidic chip that does not require bulky peripheral devices or an external power source to investigate the relationship between hepatocyte functional maintenance and flow rates. In our culture system, two types of microfluidic devices were used as scaffolds: a monolayer- and a concave chamber-based device. Under flow conditions, our chips improved albumin and urea secretion rates after 13 days compared to that of the static chips. Reverse transcription polymerase chain reaction demonstrated that hepatocyte-specific gene expression was significantly higher at 13 days under flow conditions than when using static chips. For both two-dimensional and three-dimensional culture on the chips, flow resulted in the best performance of the hepatocyte culture in vitro. We demonstrated that flow improves the viability and efficiency of long-term culture of primary hepatocytes and plays a key role in hepatocyte function. These results suggest that this flow system has the potential for long-term hepatocyte cultures as well as a technique for three-dimensional culture.
authors.affiliation: Department of HBP Surgery & Liver Transplantation, Department of Surgery, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul, 136-701, South Korea.
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Choi
authors.affiliation: Department of HBP Surgery & Liver Transplantation, Department of Surgery, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul, 136-701, South Korea.
authors.forename: Jaehyung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of HBP Surgery & Liver Transplantation, Department of Surgery, Korea University College of Medicine, 145 Anam-ro, Seongbuk-gu, Seoul, 136-701, South Korea. kimds1@korea.ac.kr.
authors.forename: Dong-Sik
authors.identifier: 0000-0002-0608-1580
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002470:Cell Survival; D002478:Cells, Cultured; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D005069:Evaluation Studies as Topic; D022781:Hepatocytes / Q000166:cytology*; D056656:Lab-On-A-Chip Devices; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D004129:Dimethylpolysiloxanes; D012709:Serum Albumin; C013830:baysilon; D014508:Urea
keywords: Hepatocyte; Microfluidic; Shear stress; Spheroid