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Hiroshi Mizumoto Last modified date:2018.05.28

Associate Professor / Molecular and Biochemical Systems Engineering
Department of Chemical Engineering
Faculty of Engineering


Graduate School
Undergraduate School


E-Mail
Homepage
http://www-lab6.chem-eng.kyushu-u.ac.jp/lab6HP/
Description about our research, publications and members .
Academic Degree
Doctor of engineering
Field of Specialization
Bioengineering
Outline Activities
We have developed the original techniques of organoid formation and applied these to develop the hybrid artificial liver. We established the spheroid formation using the polyurethane foam as scaffold of cell culture and developed the hybrid artificial liver support system for clinical use of acute liver failure. The system was applied to the large scaled animal and the clinical effectiveness was proved. We also established the maintenance of liver functions for several months using the hollow fiber as the scaffold and using the centrifugal-force-induced organoid formation and developed the hybrid artificial liver with lobule like structure for chronic liver failure.
Research
Research Interests
  • In Vitro Reconstruction of Three Dimensional Hematopoietic Microenvironment for Mouse Bone Marrow Cells Using Polyurethane Foam
    keyword : bone marrow, hematopoietic stem cell, three dimensional culture, regenerative medicine
    2006.04Study on hematopoietic stem cell in three dimensional culture.
  • Development of mass cultivation system for embryonic stem cell
    keyword : embryonic stem cell, mass cultivation system, regenerative medicine
    2005.04Study on mass cultivation system for undifferentiated ES cells Keyword: Embryonic Stem Cell, Mass Cultivation System, Regenerative Medicine.
  • Development of hybrid artificial liver support system
    keyword : hybrid artificial liver, bioreactor, artificial organs, regenerative medicine, hepatocyte, stem cell
    2000.04Study on Development of Hybrid Artificial Liver Support System (HALSS) We have developed two types of HALSS that use hepatocyte organoid culture. One is a PUF-HALSS comprising a bioreactor using polyurethane foam (PUF). In the bioreactor hepatocytes were immobilized in the pores of PUF and formed spheroid, and maintained liver-specific functions for at least ten days in vitro. The other is a LLS-HALSS that used a bioreactor containing hollow fibers with a microregular arrangement. Hepatocytes were immobilized in the extracapillary space and formed organoids by centrifugation. LLS-HALSS achieved long term maintenance of liver-specific functions for at least two months in vitro. In animal experiments, each HALSS was effective in supporting liver function, stabilization of general conditions and recovery from liver failure state. These results indicate that these HALSS may be useful to treat liver failure patients until liver transplantation or until regeneration of the native liver. Keyword: Hybrid Artificial Liver, Bioreactor, Artificial Organ, Stem Cell.
  • Development of three dimensional culture system for animal cells and application to regenerative medicine technology
    keyword : three dimensional culture, multicellular organoid, regenerative medicine, stem cell
    2000.04Study on Development of a Three Dimensional Organoid Culture System Keyword: Three Dimensional Culture, Organoid, Regenerative Medicine, Stem Cell.
Academic Activities
Books
1. Hiroshi Mizumoto, Nana Shirakigawa, Hiroyuki Ijima, Current Status and New Challenges of the Artificial Liver (in: Biomedical Engineering Challenges: A Chemical Engineering Insight), Wiley, pp. 27-54, 2018.02.
2. Bioengineering and Biomedical Engineering: 6.2 Artificial Organs, H. Mizumoto, T. Kajiwara, K. Funatsu, CORONA PUBLISHING CO., LTD., pp.201-210, April, 2006.
3. Shokuhin Setsubi, Kiki-Jiten: Chap. 6 Large-Scale Cell Culture System, H. Mizumoto, K. Funatsu, Industrial Research Center of Japan, Inc., pp.400-404, July, 2002.
Reports
1. Hybrid artificial liver using hepatocyte organoid, H. Mizumoto, K. Nakazawa, H. Ijima, K. Funatsu, T. Kajiwara, Regenerative Medicine, Vol. 5, pp.389-394, August, 2006.
2. Development of a hybrid artificial liver using hepatocyte organoid culture, K. Aoki, H. Mizumoto, K. Nakazawa, T. Kajiwara, K. Funatsu, Book Chemical Engineering Symposium Series 79, pp. 80-83, January, 2006.
3. Development of Hybrid Artificial Liver Using Hollow Fiber, H. Mizumoto, K. Nakazawa, T. Kajiwara, K. Funatsu, Seikei-Kakou, Vol.14, No.12, pp.781-786, December, 2002.
Papers
1. 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, https://doi.org/10.14326/abe.7.18, 7, 0, 18-27, 2018.01, The liver plays a central role in all metabolic processes in our body. Currently, orthotropic liver transplantation is the only proven effective treatment for serious acute liver failure (ALF) such as fulminant hepatic failure (FHF). However, liver transplantation has not yet become a standard treatment for FHF because of a shortage of donors. A bioartificial liver (BAL) device containing living hepatocytes might be a therapeutic alternative to liver transplantation. In this study, we developed a hollow fiber (HF)-type bioartificial liver (BAL) module and evaluated the performance of an embryonic stem cell (ESC)-immobilized bioartificial liver (ES-BAL) module in vitro and ex vivo. Mouse ESCs were immobilized in a BAL module and then cultured under perfusion conditions. Cells immobilized inside the HFs had a high proliferative activity and formed cylindrical organoids. For hepatic differentiation of cultured cells, differentiation-promoting agents were added to the culture medium. Ammonia removal and albumin secretion were detected after about 2 weeks of culture. Male Wistar rats were used in animal experiments. After induction of liver failure, rats were connected to an ES-BAL module containing differentiated ESCs or a control module (without cells) and underwent extracorporeal circulation for 1 h. We measured the changes in blood biochemical parameters. All rats in the control group died within 10 h, whereas two out of three rats treated with the ES-BAL module recovered after the operation. We evaluated the changes in blood biochemical parameters and the liver weight of surviving rats treated with the ES-BAL module. Most of the blood biochemical parameters had returned to normal ranges at 1 week after treatment. We also observed increased liver weight. In conclusion, we developed a novel HF-type BAL module containing differentiated ESCs with liver-specific functions. Our BAL module has the potential to support liver functions and induce liver regeneration in rats with liver failure..
2. 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, 21, 2-3, 421-428, 2012.02.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. H. Mizumoto, K. Funatsu, Liver regeneration by using a hybrid artificial liver, Artificial Organs, Vol. 12, No. 1, 51-58, 2004.01.
Presentations
1. Hiroshi Mizumoto, Tatsuya Okudaira, Ryohei Yabuta, Toshihisa Kajiwara, Functional and structural analysis of a fiber-type hepatic tissue fabricated by a bottom-up method using multilayer spheroids, TERMIS AP 2017, 2017.09.
2. Hiroshi Mizumoto, Sakiko Matsushita, Toshihisa Kajiwara, Generation of functional hepatocyte-like cells from human induced pluripotent stem cells in a three-dimensional culture using hollow fibers., Tissue Engineering & Regenerative Medicine International Society-Americas Meeting 2016, 2016.12.
3. Hiroshi Mizumoto, Hirofumi Nagayama, Naoki Amimoto, Toshihisa Kajiwara, Scalable expansion of pluripotent stem cells in a three-dimensional culture using hollow fibers., Tissue Engineering & Regenerative Medicine International Society-Americas Meeting 2016, 2016.12.
4. Hiroshi Mizumoto, Hirofumi Nagayama, Yusuke Takasuka, Naoki Amimoto, A Hollow Fiber Culture Device for Large Scale Cultivation of Pluripotent Stem Cells, The 29th Annual and International Meeting of Japanese Association for Animal Cell Technology, 2016.11.
5. Hiroshi Mizumoto, Hirofumi Nagayama, Naoki Amimoto, Yusuke Takasuka, Toshihisa Kajiwara, A three-dimensional culture using hollow fibers for large scale expansion of pluripotent stem cells, The 22nd Symposium of Young Asian Biological Engineers' Community, 2016.10.
6. Hiroshi Mizumoto, Tatsuya Okudaira, Yuki Naruo, Toshihisa Kajiwara, An approach for formation of vascularized hepatic tissue by self-assembly of multicellular spheroids covered with endothelial cells, The 21st Symposium of Young Asian Biochemical Engineering Community, 2015.10.
7. Hiroshi Mizumoto, Tatsuya Okudaira, Yuki Naruo, Toshihisa Kajiwara, An approach for fabrication of vascularized hepatic tissue by self-assembly of multicellular spheroids, The International Forum on MicroManufacturing & Biofabrication 2015, 2015.05.
8. Hiroshi Mizumoto, Shinya Iwanaga, Ken Yamada, Yuka Shidahara, Naoki Amimoto, Toshihisa Kajiwara, Generation of hematopoietic cells from embryonic stem cells in a three dimensional culture inside hollow fibers, The 27th Annual Meeting of Japanese Association for Animal Cell Technology (JAACT 2014), 2014.11.
9. Hiroshi Mizumoto, Hirofumi Nagayama, Naoki Amimoto, Kazunori Toma, Toshihisa Kajiwara, Scalable expansion of embryonic stem cells in hollow fiber bioreactor, The 27th Annual Meeting of Japanese Association for Animal Cell Technology (JAACT 2014), 2014.11.
10. Hiroshi Mizumoto, Tatsuya Okudaira, Naoki Amimoto, Toshihisa Kajiwara, Evaluation of a three-dimensional hepatic tissue fabricated by stacking endothelial cells covered hepatocyte spheroids, 2014 Tissue Engineering and Regenerative Medicine International Society Asia-Pacific Annual Conference (TEMRIS-AP 2014), 2014.09.
11. Hiroshi Mizumoto, Naoki Amimoto, Hirofumi Nagayama, Kazunori Toma, Toshihisa Kajiwara, Scalable expansion of embronic stem cells in a three-dimensional culture using hollow fibers, 2014 Tissue Engineering and Regenerative Medicine International Society Asia-Pacific Annual Conference (TEMRIS-AP 2014), 2014.09.
12. Hiroshi Mizumoto, Kana Dohji, Toshihisa Kajiwara, Effects of hydrodynamics on undifferentiated mouse ES cells proliferation in a suspension bioreactor, 3rd TERMIS World Congress 2012, 2012.09.
13. Hiroshi Mizumoto, Toshihisa Kajiwara, EXPANSION OF UNDIFFERENTIATED MOUSE EMBRYONIC STEM CELLS IN SUSPENSION BIOREACTOR ON VARIOUS SHEAR CONDITIONS, International Society for Stem Cell Research (ISSCR) 10th Annual Meeting, 2012.06.
Membership in Academic Society
  • The Japanese Society for Regenerative Medicine
  • Japanese Society of Alternative to Animal Experiments
  • Japanese Association for Animal Cell Technology
  • Japanese Society for Artificial Organs
  • The Society of Chemical Engineers, Japan
Awards
  • The SCEJ technology Award, April, 2004
  • Japanese Society for Artificial Organs Original Award, November, 2001
Educational
Educational Activities
Cell Biology
Introduction of Chemical Process and Biotechnology, Unit Operation
Basic Biotechnology
Biochemical Engineering
Cell Culture Engineering, Advanced Course