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水本 博（みずもと ひろし） データ更新日：2024.04.17

准教授　／　 工学研究院 化学工学部門 分子・生物システム工学


原著論文
1. Yoshida Kozue, Nakamura Shunsuke, Sakamoto Hiroki, Kondo Mika, Chouno Takehiro, Ikegami Yasuhiro, Shirakigawa Nana, Mizumoto Hiroshi, Yamashita Yo ichi, Baba Hideo, Ijima Hiroyuki, Normothermic machine perfusion system satisfying oxygen demand of liver could maintain liver function more than subnormothermic machine perfusion., Journal of Bioscience and Bioengineering, 10.1016/j.jbiosc.2020.08.011, 131, 1, 107-113, 2020.10.
2. Yusuke Fujii, Kengo Higashi, Hiroshi Mizumoto, Masamichi Kamihira, Toshihisa Kajiwara, A bioartificial liver device based on three-dimensional culture of genetically engineered hepatoma cells using hollow fibers, Cytotechnology, 10.1007/s10616-020-00372-0, 72, 2, 227-237, 2020.04, [URL], The bioartificial liver (BAL) device is an extracorporeal liver support system incorporating living hepatocytes. A major problem in BAL device development is to obtain a high number of functional cells. In this study, we focused on a genetically engineered mouse hepatoma cell line, Hepa/8F5, in which elevated liver functions are induced via overexpression of liver-enriched transcription factors activated by doxycycline (Dox) addition. We applied a three-dimensional culture technique using hollow fibers (HFs) to Hepa/8F5 cells. Hepa/8F5 cells responded to Dox addition by reducing their proliferative activity and performing liver-specific functions of ammonia removal and albumin secretion. The functional activities of cells depended on the timing of Dox addition. We also found that Hepa/8F5 cells in the HF culture were highly functional in a low rather than high cell density environment. We further fabricated an HF-type bioreactor with immobilized Hepa/8F5 cells as a BAL device. Although ammonia removal activity of this BAL device was lower than that of the small-scale HF bundle, albumin secretion activity was slightly higher. These results indicated that the BAL device with immobilized Hepa/8F5 cells was highly functional with potential to show curative effects in liver failure treatment..
3. Sakiko Matsushita, Toshihisa Kajiwara, Hiroshi Mizumoto, Expansion and differentiation of human iPS cells in a three-dimensional culture using hollow fibers and separation of the specific population by magnetic-activated cell sorting, Journal of Bioscience and Bioengineering, 10.1016/j.jbiosc.2019.03.014, 128, 4, 480-486, 2019.10, [URL], In order to employ pluripotent stem cells in the field of regenerative medicine, it is necessary to establish a large-scale culture system for cell differentiation. We have developed a novel three-dimensional method for culturing human induced pluripotent stem (iPS) cells, using hollow fibers (HFs). The cells immobilized inside HFs can proliferate and form multicellular aggregates, capable of achieving a high cell density and promoting further spontaneous cell differentiation. We first cultured human iPS cells for 7 days under conditions that maintained their undifferentiated state and then switched the culture conditions to allow spontaneous cell differentiation. In the 7-day undifferentiated culture, a high cell density of approximately 10-fold that of the initial seeding density was achieved. The upregulation of gene markers for differentiation such as CXCR4 or SOX17 was observed in the culture of differentiated cells. Expression of the lineage-specific cell-surface marker CXCR4 was about 30% at day 5 in the differentiation culture, which was 2-fold higher than that in the traditional monolayer culture. After HF culture, we obtained the CXCR4-positive cell population and performed monolayer culture for further differentiation of the hepatic lineage. In the CXCR4-positive cell population, the expression levels of a few liver-specific gene markers tended to increase. However, there were no significant differences between the separation and non-separation groups, which indicates the need for refinement of the cell separation process and cell maturation procedure in future studies. In conclusion, the HF culture method has potential for achieving the large-scale culturing and spontaneous differentiation of human iPS cells..
4. Hiroshi Mizumoto, Naoki Amimoto, Toru Miyazawa, Hideki Tani, Kaoru Ikeda, Toshihisa Kajiwara, In vitro and ex vivo Functional Evaluation of a Hollow Fiber-type Bioartificial Liver Module Containing ES Cell-derived Hepatocyte-like Cells, Advanced Biomedical Engineering, 10.14326/abe.7.18, 7, 0, 18-27, 2018.01, [URL].
5. Yu Nakano, Shinya Iwanaga, Hiroshi Mizumoto, Toshihisa Kajiwara, Evaluation of hollow fiber culture for large-scale production of mouse embryonic stem cell-derived hematopoietic stem cells, Cytotechnology, 10.1007/s10616-018-0210-z, 1-8, 2018.03, [URL].
6. Tatsuya Okudaira, Ryohei Yabuta, Hiroshi Mizumoto, Toshihisa Kajiwara, Fabrication of a fiber-type hepatic tissue by bottom-up method using multilayer spheroids, Journal of Bioscience and Bioengineering, 10.1016/j.jbiosc.2017.01.002, 123, 6, 739-747, 2017.06.
7. Damania Apeksha, Hassan Mohsin, Nana Shirakigawa, Hiroshi Mizumoto, Kumar Anupam, Sarin Shiv K., Hiroyuki Ijima, Masamichi Kamihira, Kumar Ashok, Alleviating liver failure conditions using an integrated hybrid cryogel based cellular bioreactor as a bioartificial liver support, SCIENTIFIC REPORTS, 10.1038/srep40323, 7, 2017.01.
8. Tatsuya Okudaira, Naoki Amimoto, Hiroshi Mizumoto, Toshihisa Kajiwara, Formation of three-dimensional hepatic tissue by the bottom-up method using spheroids, Journal of Bioscience and Bioengineering, in press, 2016.01.
9. Y. YAMAMOTO, A. ITO, H. JITSUNOBU, K. YAMAGUCHI, Y. KAWABE, H. MIZUMOTO, M. KAMIHIRA, Hollow Fiber Bioreactor Perfusion Culture System for Magnetic Force-Based Skeletal Muscle Tissue Engineering, Journal of Chemical Engineering of Japan, 45, 5, 348-354, 2012.05.
10. H. MIZUMOTO, S. HAYASHI, K. MATSUMOTO, K. IKEDA, T. KUSUMI, M. INAMORI, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, Evaluation of a Hybrid Artificial Liver Module Based on a Spheroid Culture System of Embryonic Stem Cell-Derived Hepatic Cells, Cell Transplantation, 10.3727/096368911X605321, 21, 2-3, 421-428, 2012.02.
11. N. AMIMOTO, H. MIZUMOTO, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, Hepatic Differentiation of Mouse Embryonic Stem Cells and Induced Pluripotent Stem Cells During Organoid Formation in Hollow Fibers, Tissue Engineering Part A, 17, 15-16, 831-839, 2011.08.
12. N. AMIMOTO, H. MIZUMOTO, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, An evaluation of the utility of the hepatic differentiation method using hollow fiber/organoid culture for the development of a hybrid artificial liver device, Biochemical Engineering Journal, 56, 2071-2078, 2011.05.
13. T. JOZAKI, K. AOKI, H. MIZUMOTO, T. KAJIWARA, In vitro reconstruction of a three-dimensional mouse hematopoietic microenvironment in the pore of polyurethane foam, Cytotechnology, 62, 6, 531-537, 2010.12.
14. M. INAMORI, H. MIZUMOTO, T. KAJIWARA, Integration of Endothelial Cell-Covered Hepatocytes Spheroids for Construction of Vascularized Liver Tissue, Animal Cell Technology: Basic & Applied Aspects (Proceedings of the 21st Annual and International Meeting of the Japanese Association for Animal Cell Technology), 16, 45-50, 2010.06.
15. T. JOZAKI, K. AOKI, H. MIZUMOTO, T. KAJIWARA, Continuous Cell Production from Three Dimensional Hematopoietic Microenvironment in Polyurethane Foam, Animal Cell Technology: Basic & Applied Aspects (Proceedings of the 21st Annual and International Meeting of the Japanese Association for Animal Cell Technology), 16, 89-94, 2010.06.
16. M. INAMORI, H. MIZUMOTO, T. KAJIWARA, Investigation of medium perfusion through scaffold-free tissue constructs using endothelial cell-covered spheroids in vitro, Biochemical Engineering Journal, 50, 3, 116-121, 2010.05.
17. M. INAMORI, H. MIZUMOTO, T. KAJIWARA, Vascularized Liver Tissue Construction In Vitro for Development of Bioassay System for Environmental Mutagenesis, Proceedings of The 3rd International Symposium on Novel Carbon Resource Sciences, 306-311, 2009.11.
18. M. INAMORI, H. MIZUMOTO, T. KAJIWARA, An Approach for Formation of Vascularized Liver Tissue by Endothelial Cell-covered Hepatocyte Spheroid Integration, Tissue Engineering Part A, Vol. 15, No. 8, pp. 2029-2037, 2009.08.
19. T. KUSUMI, K. ISHIHARA, H. MIZUMOTO, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, Evaluation of A Bioreactor with Stacked Sheet Shaped Organoids of Primary Hepatocytes, Journal of Bioscience and Bioengineering, Vol. 107, No. 5, pp.552-555, 2009.05.
20. H. MIZUMOTO, K. ISHIHARA, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, A New Culture Technique for Hepatocyte Organoid Formation and Long-Term Maintenance of Liver Specific Functions, Tissue Engineering Part C: Methods, Vol. 14, No. 2, pp. 167-175, 2008.06.
21. Y. IRIE, H. MIZUMOTO, S. FUJINO, T. KAJIWARA, Reconstruction of Cartilage Tissue Using Scaffold-Free Organoid Culture Technique, Journal of Bioscience and Bioengineering, Vol. 105, No. 5, pp.450-453, 2008.05.
22. K. MATSUMOTO, H. MIZUMOTO, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, Hepatic Differentiation of Mouse Embryonic Stem Cells in a Three-Dimensional Culture System Using Polyurethane Foam, Journal of Bioscience and Bioengineering, Vol. 105, No. 4, pp.350-354, 2008.04.
23. Y. IRIE, H. MIZUMOTO, S. FUJINO, T. KAJIWARA, Development of Articular Cartilage Grafts Using Organoid Formation Techniques, Transplantation Proceedings, Vol. 40, No. 2, pp. 631-633, 2008.03.
24. K. MATSUMOTO, H. MIZUMOTO, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, Hepatic Differentiation of Mouse Embryonic Stem Cells in a Bioreactor Using Polyurethane/Spheroid Culture, Transplantation Proceedings, Vol. 40, No. 2, pp. 614-616, 2008.03.
25. H. MIZUMOTO, K. AOKI, K. NAKAZAWA, H. IJIMA, K. FUNATSU, T. KAJIWARA, Hepatic Differentiation of Embryonic Stem Cells in HF/Organoid Culture, Transplantation Proceedings, Vol. 40, No. 2, pp. 611-613, 2008.03.
26. K. AOKI, H. MIZUMOTO, K. NAKAZAWA, K. FUNATSU, T. KAJIWARA, Evaluation of a hybrid artificial liver module with liver lobule-like structure in rats with liver failure, The International Journal of Artificial Organs, Vol. 31, No. 1, pp.55-61, 2008.02.
27. K. AOKI, K. NODA, H. MIZUMOTO, K. NAKAZAWA, K. FUNATSU, T. KAJIWARA, Development of A Hybrid Artificial Liver Module With Hepatocyte Organoids Induced by Centrifugal Force, Proceedings of 2006 Japan/Taiwan/Korea Chemical Engineering Conference, pp.19-20, 2006.11.
28. K. Ishihara, H. Mizumoto, K. Nakazawa, T. Kajiwara, K. Funatsu, Formation of a sheet-shaped organoid using rat primary hepatocytes for long-term maintenance of liver-specific functions, The International Journal of Artificial Organs, Vol.29, No.3, 318-328, 2006.03.
29. J. Fukuda, K. Okamura, K. Ishihara, H. Mizumoto, K. Nakazawa, H. Ijima, T. Kajiwara, K. Funatsu, Differentiation Effects by the Combination of Spheroid Formation and Sodium Butyrate Treatment in Human Hepatoblastoma Cell Line (Hep G2): A Possible Cell Source for Hybrid Artificial Liver, Cell Transplantation, Vol.14, No. 10, pp.819-827, 2006.03.
30. J. Fukuda, H. Mizumoto, K. Nakazawa, T. Kajiwara, K. Funatsu, Hepatocyte organoid culture in elliptic hollow fibers to develop a hybrid artificial liver, The International Journal of Artificial Organs, 27, 12, 1091-1099, Vol.27, No. 12, pp.1091-1099, 2004.12.
31. H. Mizumoto, T. Yamaguchi, K. Aoki, K. Nakazawa, T. Kajiwara, K. Funatsu, Development of a hybrid artificial liver module having liver lobule-like strucuture, The 10th Asian Pacific Confederation of Chemical Engineering Congress, pp.1-7, 2004.10.
32. K. Ishihara, J. Fukuda, H. Mizumoto, K. Nakazawa, T. Kajiwara, K. Funatsu, Organoid-sheet formation for hepatocyte and myocardial cell culture, The 10th Asian Pacific Confederation of Chemical Engineering Congress, pp.1-9, 2004.10.
33. H. Mizumoto, K. Funatsu, Liver regeneration by using a hybrid artificial liver, Artificial Organs, Vol. 12, No. 1, 51-58, 2004.01.
34. R. Sakiyama, K. Nakazawa, H. Ijima, H. Mizumoto, T. Kajiwara, M. Ito, H. Ishibashi, K. Funatsu, Recovery of rats with fulminant hepatic failure by using a hybrid artificial liver support system with polyurethane foam/rat hepatocyte spheroids, The International Journal of Artificial Organs, 25, 12, 1144-1152, Vol. 25, No. 12, 1144-1152, 2002.12.
35. 中澤浩二，水本　博，井嶋博之，船津和守, 肝細胞組織体の新規形成法と肝小葉類似構造を有する新規人工肝臓モジュールの開発, 人工臓器, Vol. 31, No. 1, 23-24, 2002.06.
36. H. Mizumoto, M. Hayakami, K. Nakazawa, H. Ijima, K. Funatsu, Formation of Cylindrical Multicellular Aggregate (Cylindroid) and Expression of Liver Specific Functions of Primary Rat Hepatocytes, Cytotechnology, 10.1023/A:1008092710307, 31, 1-2, 69-75, Vol. 31,69-75, 1999.11.
37. K. Nakazawa, H. Mizumoto, M. Kaneko, H. Ijima, T. Gion, M. Shimada, K. Shirabe, K. Takenaka, K. Sugimachi, K. Funatsu, Formation of Porcine Hepatocyte Spherical Multicellular Aggregates (Spheroids) and Analysis of Drug Metabolic Functions, Cytotechnology, 10.1023/A:1008040726236, 31, 1-2, 61-68, Vol. 31, 61-68, 1999.11.
38. H. Mizumoto, M. Kaneko, K. Nakazawa, H. Ijima, T. Matsushita, K. Funatsu, Formation of Cylindrical Multicellular Aggregate (Cylindroid) of Rat Hepatocytes on Preed Sheet of Polyurethane Foam, Animal Cell Technology: Basic & Applied Aspects, 229-233, Vol. 10, 229-233, 1999.05.
39. H. Ijima, K. Nakazawa, H. Mizumoto, T. Matsushita, K. Funatsu, Formation of a Spherical Multicellular Aggregate (Spheroid) of Animal Cells in the Pores of Polyurethane Foam as a Cell Culture Substratum and Its Application to a Hybrid Artificial Liver, Journal of Biomaterial Science, 10.1163/156856298X00136, 9, 7, 765-778, Vol. 9, No. 7, 765-778, 1998.07.
40. H. Ijima, K. Nakazawa, M. Kaneko, H. Mizumoto, T. Matsushita, T. Gion, M. Shimada, K. Shirabe, K. Takenaka, K. Sugimachi, K. Funatsu, The Formation of a Primary Hepatocytes Spheroid and the Expression of Liver Specific Functions Depend on the Characteristics of Polyurethane Foam, Journal of Artificial Organs, Vol. 1, No. 283-88, 1998.12.
41. K. Nakazawa, T. Matsushita, H. Mizumoto, K. Funatsu, Development of Drug Metabolism Simulator Using Three-Dimensional Culture of Hepatocytes -Lidocaine and Acetaminophen Metabolism in Rat Hepatocyte/Spheroid Culture-, Animal Cell Technology: Basic & Applied Aspects, 291-296, Vol.8, pp.291-296, 1997.06.
42. 中澤浩二，水本博，井嶋博之，松下琢，船津和守, PUF／肝細胞スフェロイド培養法を利用した薬物代謝シミュレ−タの開発−人工肝臓装置によるアセトアミノフェン代謝の研究, 人工臓器, Vol. 26，No. 3, pp.713-718, 1997.06.
43. K. Funatsu, K. Nakazawa, H. Mizumoto, K. Takenaka, T. Matsushita, Development of Drug Metabolism Simulator Using Three-Dimensional Culture of Hepatocytes of Rats and Dogs -Lidocaine Metabolism in Hepatocyte/Spheroid Culture of Rats and Dogs-, Animal Cell Technology: From Vaccines to Genetic Medicine, 85-90, pp.85-90, 1996.12.


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