Development of a Perfusing Small Intestine–Liver Microphysiological System Device
There is an increasing need to develop alternatives to animal modeling and testing for pre-clinical studies as researchers face major challenges, such as the study of dynamic systems in laboratory settings. Microphysiological system (MPS) technology has recently shown great potential for addressing...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2076-3417/13/18/10510 |
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| author | Yoko Sakai Masanari Matsumura Hideki Yamada Atsushi Doi Isao Saito Takahiro Iwao Tamihide Matsunaga |
| author_facet | Yoko Sakai Masanari Matsumura Hideki Yamada Atsushi Doi Isao Saito Takahiro Iwao Tamihide Matsunaga |
| author_sort | Yoko Sakai |
| collection | DOAJ |
| description | There is an increasing need to develop alternatives to animal modeling and testing for pre-clinical studies as researchers face major challenges, such as the study of dynamic systems in laboratory settings. Microphysiological system (MPS) technology has recently shown great potential for addressing such limitations. We developed a perfusing small intestine–liver-connected device that is easy to operate and highly reproducible. In non-clinical pharmacokinetics and safety studies, the use of human-derived materials is necessary. We used human iPS cell-derived small intestinal epithelial cells (HiEs) and cryopreserved human primary hepatocytes. Hepatocytes in 3D culture were co-cultured with swiss-albino 3T3 cells as feeder cells. We evaluated the effects of co-culturing hepatocytes and HiEs using our small intestine–liver device. The mRNA expression levels of CYP1A2 and CYP3A4 in hepatocytes were significantly increased in the 3D culture. The TEER values were increased in HiEs co-cultured with hepatocytes in the 3D culture. We evaluated the differential proliferation and function characteristics of the hepatocytes and HiEs following perfusion and verified the utility of our proposed small intestine–liver device for evaluating multiple cell populations. The perfusion culture system of our small intestine–liver device can be used to investigate distinct effects on co-cultured hepatocytes and HiEs. |
| first_indexed | 2024-03-10T23:04:05Z |
| format | Article |
| id | doaj.art-fcdd1806848f43bcb45bc99bca525fdf |
| institution | Directory Open Access Journal |
| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-10T23:04:05Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Applied Sciences |
| spelling | doaj.art-fcdd1806848f43bcb45bc99bca525fdf2023-11-19T09:28:47ZengMDPI AGApplied Sciences2076-34172023-09-0113181051010.3390/app131810510Development of a Perfusing Small Intestine–Liver Microphysiological System DeviceYoko Sakai0Masanari Matsumura1Hideki Yamada2Atsushi Doi3Isao Saito4Takahiro Iwao5Tamihide Matsunaga6Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanShinko Chemical Co., Ltd., Kanazawa 920-0346, JapanShinko Chemical Co., Ltd., Kanazawa 920-0346, JapanShinko Chemical Co., Ltd., Kanazawa 920-0346, JapanDepartment of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanThere is an increasing need to develop alternatives to animal modeling and testing for pre-clinical studies as researchers face major challenges, such as the study of dynamic systems in laboratory settings. Microphysiological system (MPS) technology has recently shown great potential for addressing such limitations. We developed a perfusing small intestine–liver-connected device that is easy to operate and highly reproducible. In non-clinical pharmacokinetics and safety studies, the use of human-derived materials is necessary. We used human iPS cell-derived small intestinal epithelial cells (HiEs) and cryopreserved human primary hepatocytes. Hepatocytes in 3D culture were co-cultured with swiss-albino 3T3 cells as feeder cells. We evaluated the effects of co-culturing hepatocytes and HiEs using our small intestine–liver device. The mRNA expression levels of CYP1A2 and CYP3A4 in hepatocytes were significantly increased in the 3D culture. The TEER values were increased in HiEs co-cultured with hepatocytes in the 3D culture. We evaluated the differential proliferation and function characteristics of the hepatocytes and HiEs following perfusion and verified the utility of our proposed small intestine–liver device for evaluating multiple cell populations. The perfusion culture system of our small intestine–liver device can be used to investigate distinct effects on co-cultured hepatocytes and HiEs.https://www.mdpi.com/2076-3417/13/18/10510microphysiological system (MPS)cryopreserved human primary hepatocyte (hepatocytes)human iPS cell-derived small intestinal epithelial cell (HiE)perfusion culturesmall intestine–liver connected device (small intestine–liver device) |
| spellingShingle | Yoko Sakai Masanari Matsumura Hideki Yamada Atsushi Doi Isao Saito Takahiro Iwao Tamihide Matsunaga Development of a Perfusing Small Intestine–Liver Microphysiological System Device Applied Sciences microphysiological system (MPS) cryopreserved human primary hepatocyte (hepatocytes) human iPS cell-derived small intestinal epithelial cell (HiE) perfusion culture small intestine–liver connected device (small intestine–liver device) |
| title | Development of a Perfusing Small Intestine–Liver Microphysiological System Device |
| title_full | Development of a Perfusing Small Intestine–Liver Microphysiological System Device |
| title_fullStr | Development of a Perfusing Small Intestine–Liver Microphysiological System Device |
| title_full_unstemmed | Development of a Perfusing Small Intestine–Liver Microphysiological System Device |
| title_short | Development of a Perfusing Small Intestine–Liver Microphysiological System Device |
| title_sort | development of a perfusing small intestine liver microphysiological system device |
| topic | microphysiological system (MPS) cryopreserved human primary hepatocyte (hepatocytes) human iPS cell-derived small intestinal epithelial cell (HiE) perfusion culture small intestine–liver connected device (small intestine–liver device) |
| url | https://www.mdpi.com/2076-3417/13/18/10510 |
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