Research Group of Biotechnology, Division of Applied Chemistry,
Graduate School of Engineering, Hokkaido University(Prof. Takagi’s Laboratory)

Labotory of Cell Processing Engineering

Our Previous Reports

A. Animal Cell Cultivation Engineering

  • Title

    Journal, Volume, Pages (Year)

    Authors

  • Comparison of the optimal culture conditions for cell growth and tissue plasminogen activator production by human embryo lung cells on microcarriers.

    Appl. Microbiol. Biotechnol., 41, 565-570(1994).

    M. Takagi and K. Ueda

  • An oxygen supply strategy for the large-scale production of tissue plasminogen activator by microcarrier cell culture.

    J. Ferment. Bioeng., 77, 301-306(1994).

    M. Takagi, H. Okumura, T. Okada, N. Kobayashi, T. Kiyota, and K. Ueda

  • On-line continuous measurement of the oxygen consumption rate in mammalian cell culture.

    J. Ferment. Bioeng., 77, 709-711(1994).

    M. Takagi and K. Ueda

  • On-line determination of optimum time for switching from growth phase to production phase in tissue plasminogen activator production in a microcarrier cell culture.

    J. Ferment. Bioeng., 77, 655-658(1994).

    M. Takagi and K. Ueda

  • A low-serum medium with BSA and ferrous sulfate for the production of tissue plasminogen activator by human embryo lung cells.

    J. Ferment. Bioeng., 77, 394-399(1994).

    M. Takagi and K. Ueda

  • Effect of insoluble medium component on the productivity of tissue plasminogen activator by cells on microcarriers.

    J. Ferment. Bioeng., 78, 269-271(1994).

    M. Takagi, T. Kiyota, and K. Ueda

  • Effect of hydrostatic pressure on hybridoma cell metabolism.

    J. Ferment. Bioeng., 80, 619-621(1995).

    M. Takagi, K. Ohara, and T. Yoshida

  • Enhanced monoclonal antibody production by gradual increase of osmotic pressure.

    Cytotechnology, 29, 27-33 (1999).

    J. Lin, M. Takagi, Y. Qu, P. Gao, and T. Yoshida

  • Metabolic flux change in hybridoma cells under high osmotic pressure.

    J Biosci. Bioeng., 87, 255-257 (1999).

    J. Lin, M. Takagi, Y. Qu, P. Gao, and T. Yoshida

  • Starch particles modified with gelatin as novel small carriers for mammalian cells

    J. Biosci. Bioeng., 88, 693-695 (1999).

    M. Takagi, H. Hayashi, and T. Yoshida

  • The effect of osmolarity on metabolism and morphology in adhesion and suspension Chinese hamster ovary cells producing tissue plasminogen activator.

    Cytotechnology, 32, 171-179 (2000).

    M. Takagi, H. Hayashi, and T. Yoshida

  • Selective retension of active cells employing low centrifugal force at the medium change during suspension culture of Chinese hamster ovary cells producing tPA.

    J. Biosci. Bioeng., 89, 340-344 (2000).

    M. Takagi, M. Ilias, and T. Yoshida

  • Effects of shifts up and down in osmotic pressure on production of tissue plasminogen activator by Chinese hamster ovary cells in suspension

    J. Biosci. Bioeng., 91, 509-514 (2001).

    M. Takagi, T. Moriyama, and T. Yoshida

  • Effects of high concentrations of energy sources and metabolites on suspension culture of chinese hamster ovary cells producing tissue plasminogen activator

    J. Biosci. Bioeng., 91, 515-521 (2001).

    M. Takagi, H.C. Hia, J.H. Jang, and T. Yoshida

  • Effect of antioxidants on the apoptosis of CHO cells and production of tissue plasminogen activator in suspension culture

    J. Biosci. Bioeng., 91(6), 581-585 (2001).

    Z. Yun, M. Takagi, and T. Yoshida

  • Possible strategy for on-line monitoring and control of hybridoma cell culture.

    Biochemical Engineering Journal, 11, 205-209 (2002).

    Jianqiang Lin, Mutsumi Takagi, Yinbo Qu, and Toshiomi Yoshida

  • Combined addition of glutathione and iron chelators for decrease of intracellular level of reactive oxygen species and death of Chinese hamster ovary cells.

    J. Biosci. Bioeng., 95(2), 124-127 (2003).

    Z. Yun, M. Takagi, and T. Yoshida

  • Effect of static pressure on hGM-CSF production by Chinese hamster ovary cells.

    J. Biosci. Bioeng., 94(3), 271-274 (2002).

    H. Gong, M. Takagi, T. Moriyama, T. Ohno, and T. Yoshida

  • Transduction of static pressure signal to expression of hGM-CSF mRNA in CHO cells.

    J. Biosci. Bioeng., 96(1), 79-82 (2003).

    Heng Gong, Mutsumi Takagi, Toshiomi Yoshida

  • Repeated addition of insulin for dynamic control of apoptosis in serum-free culture of CHO cells.

    J. Biosci. Bioeng., 96(1), 59-64 (2003).

    Z. Yun, M. Takagi, and T. Yoshida

  • Fetal-calf-serum-free culture of Chinese hamster ovary cells employing fish serum.

    Appl. Microbiol. Biotechnol., 75, 983-987 (2007).

    M. Fujiwara, R. Tsukada, Y. Tsujinaga, and M. Takagi

  • Effect of static pressure on intracellular pH of adhesive CHO cells.

    J. Biol. Bioeng., 104(6), 510-512 (2007).

    M. Fujiwara, S. Koizumi, and M. Takagi

  • Effects of heat treatment and concentration of fish serum on cell growth in adhesion culture of Chinese hamster ovary cells.

    Cytotechnology, 59(2), 135-141 (2009).

    M. Fujiwara, R. Tsukada, I. Shioya, and M. Takagi

  • Fetal-calf-serum-free suspension culture of Chinese hamster ovary cells employing fish serum.

    J. Biol. Bioeng., 109(3), 307-309 (2010)

    M. Fujiwara, Y. Aizu, I. Shioya, and M. Takagi

     

    Design of serum-free medium for suspension culture of CHO cells on the basis of general commercial media.

    Cytotechnology, 67(4) August, 689-697 (2015)

    H. Miki and M. Takagi

B. Development of Hybrid Artificial Organs

B-1. Novel Hybrid Artificial Lung

  • Title

    Journal, Volume, Pages (Year)

    Authors

  • Oxygen transfer rate of a hybrid artificial lung model.

    Jpn. J. Artif. Organs, 25, 811-815 (1996).

    T. Inoue, M. Takagi, Y. Sawa, R. Shirakura, and T. Yoshida

  • Hybrid artificial lung with interleukin-10 and endothelial constitutive nitric oxide synthase gene-transfected endothelial cells attenuates inflammatory reactions induced by cardiopulmonary bypass.

    Circulation, 98, Ⅱ-269 - Ⅱ-274(1998).

    T. Ohata, Y. Sawa, S. Ohtake, M. Takagi, T. Inoue, T. Yoshida, and H. Matsuda

  • Enhanced adhesion of endothelial cells onto a polypropylene hollow fiber membrane by plasma discharge treatment and high inoculum cell density

    Journal of Artificial Organs, 4, 220-225 (2001).

    M. Takagi, T. Haraguchi, H. Kawai, K. Shiwaku, T. Inoue, Y. Sawa, H. Matsuda, T. Yoshida

  • Hydrodynamically stable adhesion of endothelial cells onto a polypropylene hollow fiber membrane by modification with adhesive protein.

    Journal of Artificial Organs, 6, 222-226 (2003).

    M. Takagi, K. Shiwaku, T. Inoue, Y. Shirakawa, Y. Sawa, H. Matsuda, T. Yoshida

B-2. Control of Hepatocytes Activiity by Synthetic Ligands

  • Title

    Journal, Volume, Pages (Year)

    Authors

  • Comparison of different hapatocyte cell lines for use in a hybrid artificial liver model.

    Cytotechnology, 24, 39-45 (1997).

    M. Takagi, N. Fukuda, and T. Yoshida

  • Analysis of ammonia metabolism of rat primary hepatocytes and a human hepatocyte cell line Huh 7.

    Cytotechnology, 32, 9-15 (2000).

    M. Takagi, N. Kojima, and T. Yoshida

  • Effect of galactose residue in glycolipid coated onto a dish on ammonia consumption activity of primary rat hepatocytes

    Journal of Artificial Organs, 4, 315-319 (2001).

    M. Takagi, K. Nomura, R. Sato, K. Toma, T. Yoshida

  • Effect of sugar residues in glycolipid coated onto a dish on ammonia consumption and gluconeogenesis activity of primary rat hepatocytes

    J. Biosci. Bioeng., 93, 437-439 (2002).

    M. Takagi, C. Matsuda, R. Sato, K. Toma, and T. Yoshida

  • In vitro proliferation of primary rat hepatocytes expressing ureogenesis activity by means of co-culture with STO cells

    J. Biosci. Bioeng., 94(3), 212-217 (2002).

    M. Takagi, H. Kondo, and T. Yoshida

  • Synthesis of 3, 4, 5-tris (alkyloxy) benzyl glycosides as glycolipid analogues

    J. Carbohyd. Chem., 23(6&7), 375-388 (2004).

    R. Sato, K. Toma, K. Nomura, M. Takagi, T. Yoshida, Y. Azefu, and H. Tamiaki

C. Regenerative Medicine

C-1.Ex vivo Expansion of Hematopoietic Progenitors in 3D Co-culture

  • Title

    Journal, Volume, Pages (Year)

    Authors

  • Spatial development of the cultivation of a bone marrow stromal cell line in porous carriers.

    Cytotechnology, 31, 225-231 (1999).

    M. Takagi, T. Sasaki, and T. Yoshida

  • Effect of temperature on cell population balance in Dexter's culture of murine bone marrow hematopoietic cells with stromal cells.

    J Biosci. Bioeng., 88, 200-204 (1999).

    M. Takagi, D. Kubomura, and T. Yoshida

  • The construction of an in vitro three-dimensional hematopoietic microenvironment for mouse bone marrow cells employing porous carriers

    Cytotechnology, 34, 121-130 (2000).

    Y. Tomimori, M. Takagi, and T. Yoshida

  • Three dimensional culture system of murine hematopoietic cells with spatial development of stromal cells in nonwoven fabric

    Cytotherapy, 4(3), 285-291 (2002).

    T. Sasaki, M. Takagi, T. Soma, and T. Yoshida

  • Effect of concentrations of murine stromal and hematopoietic cells on their three-dimensional coculture in nonwoven fabrics.

    J. Biosci. Bioeng., 94(4), 365-367 (2002).

    M. Takagi, N. Iemoto, and T. Yoshida

  • Analysis of hematopoietic microenvironment containing spatial development of stromal cells in nonwoven fabrics

    J. Biosci. Bioeng., 96(1), 76-78 (2003).

    T. Sasaki, M. Takagi, T. Soma, and T. Yoshida

  • Effect of pore diameter of porous membrane on progenitor content during a membrane-separated coculture of hematopoietic cells and stromal cell line.

    Journal of Artificial Organs, 6, 130-137 (2003).

    M. Takagi, K. Horii, and T. Yoshida

  • Effect of heparin addition on expansion of cord blood hematopoietic progenitors in three-dimensional coculture with stromal cells in nonwoven fabrics.

    Journal of Artificial Organs, 7(4), 194-202 (2004).

    T. Okamoto, M. Takagi, T. Soma, H. Ogawa, M. Kawakami, M. Mukubo, K. Kubo, R. Sato, K. Toma, and T. Yoshida

C-2. Regeneration of Articular Cartilage using Mesenchymal Stem Cells

  • Title

    Journal, Volume, Pages (Year)

    Authors

  • In vitro proliferation of human bone marrow mesenchymal stem cells employing donor serum and basic fibroblast growth factor.

    Cytotechnology, 43(1-3), 89-96 (2003).

    M. Takagi, T. Nakamura, C. Matsuda, T. Hattori, S. Wakitani, and T. Yoshida

  • Effect of PLGA mesh on a three-dimensional culture of chondrocytes

    J. Biosci. Bioeng, 98(6), 477-481 (2004).

    M. Takagi, Y. Fukui, S. Wakitani, and T. Yoshida

  • Effect of subcultivation of human bone marrow mesenchymal stem cells on their capacities for chondrogenesis, supporting hematopoiesis, and telomea length

    Cytotechnology, 47, 19-27 (2005).

    M. Nakahara, M. Takagi, T. Hattori, S. Wakitani, and T. Yoshida

  • Differentiation of human bone marrow mesenchymal stem cells to chondrocytes for cartilage tissue.

    Cytotechnology, 47, 11-17 (2005).

    C. Matsuda, M. Takagi, T. Hattori, S. Wakitani, and T. Yoshida

  • Effect of chondroitin sulfate and hyaluronic acid on gene expression in a three-dimensional culture of chondrocytes.

    J. Biosci. Bioeng., 100(1), 123-126 (2005).

    S. Nishimoto, M. Takagi, S. Wakitani, and T. Yoshida

  • High inoculation cell density could accelerate the differentiation of human bone marrow mesenchymal stem cells to chondrocyte cells.

    J. Biosci. Bioeng., 103(1), 98-100 (2007).

    M. Takagi, Y. Umetsu, M. Fujiwara, and S. Wakitani

  • Influence of fetal calf serum on differentiation of mesenchymal stem cells during expansion.

    J. Biosci. Bioeng., 106(1), 46-50 (2008).

    M. Yokoyama, H. Miwa, S. Maeda, S. Wakitani, and M. Takagi

  • A mass separation of chondrocytes from cartilage tissue utilizing an automatic crushing device.

    J. Biosci. Bioeng., 109(1), 73-74 (2010).

    M. Takagi, H. Yoshioka, and S. Wakitani

  • Effect of monosaccharides composing glycosaminoglycans on type 2 collagen accumulation in a three-demensional culture of chondrocytee.

    J. Biosci. Bioeng., 109(1), 51-54 (2010).

    E. Kagita, M. Ikeda, S. Wakitani, and M. Takagi

  • Combination of cytomegalovirus enhancer with human cellular promoters for gene-induced chondrogenesis of human bone marrow mesenchymal stem cells.

    J. Biol. Bioeng., 110(5), 593-596 (2010).

    R. Iwai, Y. Kumagai, M. Fujiwara, S. Wakitani, and M. Takagi

  • Ex vivo cartilage defect model for the evaluation of cartilage regeneration using mesenchymal stem cells.

    J. Biol. Bioeng., 111(3) March, 357-364 (2011).

    R. Iwai, M. Fujiwara, S. Wakitani, and M. Takagi

  • Shrinkage-free preparation of scaffold-free cartilage-like disc-shaped cell sheet using human bone marrow mesenchymal stem cells.

    J. Biol. Bioeng., 111(4) April, 489-492 (2011).

    S. Maeda, T. Fujitomo, T. Okabe, S. Wakitani, and M. Takagi

  • Construction of osteochondral-like tissue graft combining β-tricalcium phosphate block and scaffold-free centrifuged chondrocyte cell sheet.

    J. Orthopaedic Science, 16 (5) June, 613-621 (2011).

    K. Niyama, N. Ide, K. Onoue, A. Kawaguchi, T. Okabe, S. Wakitani, and M. Takagi

  • Xeno-free proliferation of human bone marrow mesenchymal stem cells.

    Cytotechnology, 64(3), 301-308 (2012).

    H. Miwa, Y. Hashimoto, K. Tensho, S. Wakitani, and M. Takagi

  • Construction of an osteochondral-like tissue graft combining β-tricalcium phosphate block and scaffold-free mesenchymal stem cell sheet.

    J. Orthopaedic Science, 18(3) May, 471-477 (2013).

    S. Miyagi, K. Tensho, S. Wakitani, and M. Takagi

  • Xeno-free and shrinkage-free preparation of scaffold-free cartilage-like disc-shaped cell sheet using human bone marrow mesenchymal stem cells.

    J. Biosci. Bioeng., 116(6) December, 734-739 (2013).

    Y. Sato, S. Wakitani, and M. Takagi

  • Noninvasive discrimination between human normal and cancer cells by analysis of intracellular distribution of phase-shift data.

    Cytotechnology, 67(4) August, 733-739 (2015).

    M. Takagi and N. Tokunaga

  • Synergistic effect of ascorbic acid and collagen addition on the increase in type 2 collagen accumulation in cartilage-like MSC sheet.

    Cytotechnology, DOI: 10.1007/s10616-015-9924-3 (2015).

    Y. Sato, H. Mera, D. Takahashi, T. Majima, N. Iwasaki, S. Wakitani, and M. Takagi

  • Transplantation of scaffold-free cartilage-like cell-sheets made from human bone marrow mesenchymal stem cells for cartilage repair: a preclinical study.

    Cartilage, accepted (2016).

    M. Itokazu, S. Wakitani, H. Mera, Y. Tamamura, Y. Sato, M. Takagi, and H. Nakamura

C-3. Noninvasive Quality Estimation of Cells under Cultivation

  • Title

    Journal, Volume, Pages (Year)

    Authors

  • Noninvasive measurement of three-dimensional morphology of adhered Chinese hamster ovary cells employing phase-shifting laser microscope.

    J. Biomed. Opt., 12(5), 54010-1-5 (2007).

    M. Takagi, T. Kitabayashi, S. Ito, M. Fujiwara, and A. Tokuda

  • Correlation between cell morphology and aggrecan gene expression level during differentiation from mesenchymal stem cells to chondrocytes.

    Biotechnology Letters., 30, 1189-1195 (2008).

    M. Takagi, T. Kitabayashi, S. Koizumi, H. Hirose, S.-i. Kondo, M. Fujiwara, K. Ueno, H. Misawa, Y. Hosokawa, and S. Wakitani

  • Correlation between cell cycle phase of adherent Chinese hamster ovary cells and laser phase shift determined by phase-shifting laser microscopy.

    Biotechnology Letters., 31, 39-42 (2009).

    S. Ito and M. Takagi

  • Noninvasive estimation of cell cycle phase and proliferation rate of human mesenchymal stem cells by phase-shifting laser microscopy.

    Cytotechnology, 59(3), 161-167 (2009).

    A. Tokumitsu, S. Wakitani and M. Takagi

  • Noninvasive discrimination of human normal cells and malignant tumor cells by phase-shifting laser microscopy.

    J. Biosci. Bioeng., 109(5), 499-503 (2010).

    A. Tokumitsu and M. Takagi

  • Quantitative correlation between production rate of melanoma inhibitory activity and aggrecan gene expression level during differentiation from mesenchymal stem cells to chondrocytes and redifferentiation of chondrocytes.

    J. Biosci. Bioeng., 111(5) May, 594-596 (2011).

    K. Onoue, H. Kusubashi, Y. Sato, S. Wakitani, and M. Takagi

  • Effect of the distance between adherent mesenchymal stem cell and the focus of irradiation of femtosecond laser on cell replication capacity.

    Cytotechnology, 64(3), 323-329 (2012).

    J. Sakai, D. Roldan, K. Ueno, H. Misawa, Y. Hosokawa, T. Iino, S. Wakitani, and M. Takagi

  • Time-lapse analysis of laser phase shift for noninvasive discrimination of human normal cells and malignant tumor cells.

    J. Biosci. Bioeng., 114(5) November, 556-559 (2012).

    M. Takagi and Y. Shibaki

  • Correlation between actin content and phase-shift of adhesive normal and malignant prostate epithelial cells.

    J. Biosci. Bioeng., 115(3) January, 310-313 (2013).

    M. Takagi and N. Tokunaga

     

    Noninvasive discrimination between human normal and cancer cells by analysis of intracellular distribution of phase-shift data.

    Cytotechnology, 67(4) August, 733-739 (2015).

    M. Takagi and N. Tokunaga

D. Cultivation Engineering of Microbes

  • Title

    Journal, Volume, Pages (Year)

    Authors

  • Effect of oleic acid adsorption onto cell surface on cholesterol oxidase production by Schizophyllum commune.

    J. Ferment. Technol., 60, 31-35(1982).

    M. Takagi, T. Yoshida, and H. Taguchi

  • Production of S-(+)-ibuprofen with high optical purity from a nitrile compound by cells immobilized on cellulose porous beads.

    J. Ferment. Bioeng., 78, 191-193(1994).

    M. Takagi, J. Shirokaze, K. Oishi, K. Otsubo, K. Yamamoto, N. Yoshida, and I. Fujimatsu

  • Production of S-(+)-ibuprofen from a nitrile compound by enzymatic reaction combined with ultrafiltration.

    J. Ferment. Bioeng., 78, 54-58(1994).

    M. Takagi, K. Oishi, F. Ishimura, and I. Fujimatsu

  • Acetone-butanol fermentation by Clostridium aurantibutyricum ATCC 17777 from a model medium for palm oil mill effluent

    J. Ferment. Bioeng., 81, 543-547(1996).

    W. Somrutai, M. Takagi, and T. Yoshida

  • Control of L-phenylalanine production by dual feeding of glucose and L-tyrosine.

    Biotechnol. Bioeng., 52, 653-660(1996).

    M. Takagi, Y. Nishio, G. Oh, and T. Yoshida

  • Control of cell growth rate by sugar feeding based on CO2 production rate.

    J. Ferment. Bioeng., 85, 354-357(1998).

    M. Takagi, F. Ishimura, and I. Fujimatsu

  • Nitrogen depletion for intracellular triglyceride accumulation to enhance liquefaction yield of marine microalgal cells into a fuel oil.

    J. Marine Biotech., 6, 44-48(1998).

    K. Yamaberi, M. Takagi, and T. Yoshida

  • Metabolism analysis and on-line physiological state diagnosis of acetone-butanol fermentation.

    Biotechnol. Bioeng., 58, 561-571(1998).

    S. Chauvatcharin, C. Siripatana, T. Seki, M. Takagi, and T. Yoshida

  • Fluid mixing and oxygen transfer in cell suspension of Taxus chinensis in a novel stirred bioreactor

    Biotechnol. Bioprocess Eng., 4, 269-272 (1999).

    Z-W. Pan, J-J. Zhong, J-Y. Wu, M. Takagi, and T. Yoshida

  • Limited feeding of potassium nitrate for intracellular lipid and triglyceride accumulation of Nannochloris sp. UTEX LB1999.

    Appl. Microbiol. Biotechnol., 54, 112-117 (2000).

    M. Takagi, K. Watanabe, K. Yamaberi, and T. Yoshida

  • Effect of mixing time on taxoid production in suspension cultures of Taxus chinensis in a centrifugal impeller bioreactor

    J. Biosci. Bioeng., 94(3), 244-250 (2002).

    Jian-Jiang Zhong, Zhi-Wei Pan, Zhen-Yu Wang, Jian-Yong Wu, Feng chen, Mutsumi Takagi, and Toshiomi Yoshida

  • Development of new dye-metal agarose-coated alumina matrix and elution strategy for purification of alcohol dehydrogenase.

    J. Biosci. Bioeng., 95(2), 133-138 (2003).

    C. Hidayat, M. Nakajima, M. Takagi, and T. Yoshida

  • Multivalent binding interaction of alcohol dehydrogenase on dye-metal affinity matrix.

    J. Biosci. Bioeng., 96(2), 168-173 (2003).

    C. Hidayat, M. Nakajima, M. Takagi, and T. Yoshida

  • Expanded bed adsorption for purification of alcohol dehydrogenase using a dye-IDA matrix.

    J. Biosci. Bioeng., 97(4), 284-287 (2004).

    C. Hidayat, M. Takagi, and T. Yoshida

  • Effect of salt concentration on intracellular accumulation of lipids and triglyceride in marine microalgae Dunaliella cells.

    J. Biosci. Bioeng.,101(3), 223-226 (2006).

    M. Takagi, Karseno and T. Yoshida

E. Others

  • Title

    Journal, Volume, Pages (Year)

    Authors