Basic studies on the development of implantable artificial liver

• Project/Area Number: 18360399
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biofunction/Bioprocess
• Research Institution: Kyushu University
• Principal Investigator: IJIMA Hiroyuki Kyushu University, 大学院・工学研究院, 准教授 (10274515)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥17,870,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥2,370,000); Fiscal Year 2008: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2007: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2006: ¥7,600,000 (Direct Cost: ¥7,600,000)
• Keywords: 人工肝臓 / 共培養 / 肝細胞 / 類洞内皮細胞 / 細胞外マトリックス / 肝細胞増殖因子 / アルブミン合成 / 薬物代謝 / 肝非実質細胞 / コラーゲンゲル / 組織体

Research Abstract

肝細胞と類洞内皮細胞との共培養は有効だが、肝機能発現に対しては、肝細胞の球状組織体包埋コラーゲンゲル培養が最も優れていた。肝細胞増殖因子/ヘパリンの共固定化基材上において肝細胞の組織形成と機能発現は有意に向上した。そこで生体温和な酵素を利用した細胞包埋ヒドロゲル充填多孔質スカッフォルド培養系を開発し、良好な肝機能発現と力学強度の保持を実現した。さらに、移植実験において新生肝組織構築の基盤技術を開発した。

Research Products

• [Journal Article] Development of a practical small-scale circulation bioreactor and application to a drug metabolism simulator (2009)
  • Author(s): Hiroyuki Ijima, Yasuo Kakeya, Takahiro Ogata, Takanori Sakai
  • Journal Title: Biochemical Engineering Journal 44 Pages: 292-296
  • Peer Reviewed
• [Journal Article] Monolayer culture of primary rat hepatocytes on an Arg-Gly-Asp (RGD)-immobilized polystyrene dish express liver-specific functions of albumin production and p-acetamidophenol metabolism the same as for spheroid culture (2009)
  • Author(s): Hiroyuki IJIMA, Yasuo KAKEYA
  • Journal Title: Biochemical Engineering Journal 40 Pages: 387-391
  • Peer Reviewed
• [Journal Article] Development of a practical small-scale circulation bioreactor and application to a drug metabolism simulator (2009)
  • Author(s): Hiroyuki Ijima, et al.
  • Journal Title: Biochemical Engineering Journal 44 Pages: 292-296
  • Peer Reviewed
• [Journal Article] Composition of culture medium is more important than CO-Culture with hepatic non-parenchymal cells in albumin production activity of primary rathepatocytes, and the effect was enhanced by hepatocytes spheroid culture in collagen gel (2009)
  • Author(s): Hiroyuki Ijima, et al.
  • Journal Title: Biochemical Engineering Journal (in press)
  • Peer Reviewed
• [Journal Article] The mixed coculture effect of primary rat hepatocytes and bone marrow cells is caused by soluble factors derived from bone marrow cells (2008)
  • Author(s): Hiroyuki IJIMA, Takeshi MATSUO, Koei KAWAKAMI
  • Journal Title: Journal of Bioscience and Bioengineering 105 Pages: 226-231
  • NAID: 110006632554
  • Peer Reviewed
• [Journal Article] Monolayer culture of primary rat hepatocytes on an Arg-Gly-Asp (RGD)-immobilized polystyrene dish express liver-specific functions of albumin production and p-acetamidophenol metabolism the same as for spheroid culture (2008)
  • Author(s): Hiroyuki Ijima, et al.
  • Journal Title: Biochemical Engineering Journal 40 Pages: 387-391
  • Peer Reviewed
• [Journal Article] The mixed coculture effect of primary rat hepatocytes and bone marrow cells is caused by soluble factors derived from bone marrow cells (2008)
  • Author(s): Hiroyuki Ijima, et. al.
  • Journal Title: Journal of Bioscience and Bioengineering 105 Pages: 226-231
  • NAID: 110006632554
  • Peer Reviewed
• [Journal Article] Monolayer culture of primary rat hepatocytes on an Arg-Gly-Asp(RGD)-immobilized polystyrene dish express liver-specific functions of albumin production and p-acetamidophenol metabolism the same as for spheroid culture (2008)
  • Author(s): Hiroyuki Ijima, et. al.
  • Journal Title: Biochemical Engineering Journal (In press)
  • Peer Reviewed
• [Journal Article] Spheroid formation and expression of liver specific function of primary rat hepatocytes co-cultured with hepatic non-parenchymal cells (2007)
  • Author(s): H.Ijima, et al.
  • Journal Title: Proceedings of the ASAIO 53^<rd> Annual Conference (in press)
• [Journal Article] Expression and maintenance of liver specific function of primary rat hepatocytes co-cultured with hepatic non-parenchymal cells in collagen gel (2007)
  • Author(s): H.Ijima, et al.
  • Journal Title: Proceedings of the TERMIS NA 2007 Conference (in press)
• [Journal Article] Composition of culture medium is more important than co-culture with hepatic non-parenchymal cells in albumin production activity of primary rat hepatocytes, and the effect was enhanced by hepatocytes spheroid culture in collagen gel
  • Author(s): Hiroyuki Ijima, Yasuo Kakeya, Toru Yokonuma, Yung-Te Hou, Takayuki Takei
  • Journal Title: Biochemical Engineering Journal (in press)
  • Peer Reviewed
• [Presentation] 肝細胞増殖因子を固定化した培養基材における初代ラット肝細胞の組織形成と機能発現 (2009)
  • Author(s): 井嶋博之、侯詠徳、尾方良平、久保孝文、松本峻一、武井孝行、境慎司、川上幸衛、
  • Organizer: 第8回日本再生医療学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2009-03-05
• [Presentation] 肝細胞増殖因子を固定化した培養基材における初代ラット肝細胞の組織形成と機能発現 (2009)
  • Author(s): 井嶋博之, 他
  • Organizer: 第8回日本再生医療学会総会
  • Place of Presentation: 東京国際フォーラム.
  • Year and Date: 2009-03-05
• [Presentation] Effect of immobilized hepatocyte growth factor on albumin secretion activity and spheroid formation in hepatocyte culture (2008)
  • Author(s): Yung-Te HOU, Takayuki TAKEI, Shinji SAKAI, Hiroyuki IJIMA, Koei KAWAKAMI
  • Organizer: The 21th International Symposium on Chemical Engineering
  • Place of Presentation: 佐賀大学
  • Year and Date: 2008-12-06
• [Presentation] Effect of immobilized hepatocyte growth factor on albumin secretion activity and spheroid formation in hepatocyte culture (2008)
  • Author(s): Yung-Te Hou, et al.
  • Organizer: The 2lth International Symposium on Chemical Engineering
  • Place of Presentation: 佐賀大学
  • Year and Date: 2008-12-06
• [Presentation] Effect of immobilized hepatocyte growth factor on albumin secretion and spheroid formation of hepatocyte in 2-dimensional culture (2008)
  • Author(s): Y. -T. Hou, T. Takei, S. Sakai, H. Ijima and K. Kawakami
  • Organizer: The 21st Annual and International Meeting of the Japanese Association for Animal Cell Technology
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2008-11-26
• [Presentation] HGF-ヘパリン固定化コラーゲンフィルム上における初代ラット肝細胞培養 (2008)
  • Author(s): 久保孝文、武井孝行、境慎司、井嶋博之、川上幸衛
  • Organizer: 化学工学会姫路大会
  • Place of Presentation: ホテル日航姫路
  • Year and Date: 2008-11-17
• [Presentation] HGF・ヘパリン固定化コラーゲンフィルム上における初代ラット肝細胞培養 (2008)
  • Author(s): 久保孝文, 他
  • Organizer: 化学工学会姫路大会
  • Place of Presentation: ホテル日航姫路
  • Year and Date: 2008-11-17
• [Presentation] 肝組織工学構築を目指した基礎的研究 (2008)
  • Author(s): 井嶋博之、掛谷泰雄、尾方良平、久保孝文、侯詠徳、境慎司、川上幸衛
  • Organizer: 第41回九大生体材料・力学研究会
  • Place of Presentation: 九州大学、福岡市
  • Year and Date: 2008-03-21
• [Presentation] 肝組織工学を目指した肝細胞共培養スフェロイド形成と装置化に向けた基礎的検討 (2008)
  • Author(s): 井嶋博之、掛谷泰雄、尾方良平、侯詠徳、久保孝文、境慎司、川上幸衛
  • Organizer: 第7回に本再生医療学会総会
  • Place of Presentation: 名古屋国際会議場、名古屋市
  • Year and Date: 2008-03-13
• [Presentation] Hepatocyte Growth Factor Enhances Spheroid Formation of Primary Rat Hepatocytes and Expression of Albumin Production Activity (2008)
  • Author(s): Yung-Te Hou, Takafumi Kubo, Shinji Sakai, Hiroyuki Ijima, Koei Kawakami
  • Organizer: 8th World Biomaterials Congress
  • Place of Presentation: Amsterdam (Netherlands)
• [Presentation] Formation of Co-cultured Hepatocyte Spheroid Which Aimed at Liver Tissue Engineering, and Preliminary Study for the Device (2008)
  • Author(s): Hiroyuki Ijima, Yasuo Kakeya, Ryohei Ogata, Yung-Te Hou, Takafumi Kubo, Shinji Sakai, Koei Kawakami
  • Organizer: 8th World Biomaterials Congress
  • Place of Presentation: Amsterdam (Netherlands)
• [Presentation] Development of hepatocyte co-culture method which aimed at liver tissue engineering, and preliminary study for the device (2007)
  • Author(s): Hiroyuki Ijima, Yasuo Kakeya, Ryohei Ogata, Yung-Te Hou, Takafumi Kubo, Toru Yokonuma, Shinji Sakai, Koei Kawakami
  • Organizer: TERMIS-AP 2007 (Tissue Engineering International & Regenerative Medicine Society, Asia-Pacific Chapter Meeting 2007)
  • Place of Presentation: Grand Prince Hotel Akasaka, Tokyo
  • Year and Date: 2007-12-03
• [Presentation] Development of hepatocyte co-culture method which aimed at liver tissue engineering,and preliminary study for the device (2007)
  • Author(s): Hiroyuki Ijima, et. al.
  • Organizer: TERMIS-AP 2007(Tissue Engineering International & Regenerative Medicine Society, Asia-Pacific Chapter Meeting 2007)
  • Place of Presentation: Grand Prince Hotel Akasaka, Tokyo
  • Year and Date: 2007-12-03
• [Presentation] ヒドロゲル充填多孔質担体の開発と肝細胞培養基材としての性能評価 (2007)
  • Author(s): 尾方良平、境慎司、井嶋博之、川上幸衛
  • Organizer: 第14回日本生物工学会九州支部大会(長崎大会)
  • Place of Presentation: 長崎大学、長崎市
  • Year and Date: 2007-12-01
• [Presentation] Development of co-culture method for primary rat hepatocytes based on collagen gel culture (2007)
  • Author(s): Yasuo Kakeya, Toru Yokonuma, Shinji Sakai, Hiroyuki Ijima, and Koei Kawakami
  • Organizer: The 20th International Symposium on Chemical Engineering, Daejeon /Chungnam (Korea)-Kyushu (Japan)
  • Place of Presentation: Hanbat National University, Daejeon, Korea
  • Year and Date: 2007-12-01
• [Presentation] Development of co-culture method for primary rat hepatocytes based on collagen gel culture (2007)
  • Author(s): Yasuo Kakeya, et. al.
  • Organizer: The 20^<th> International Symposium on Chemical Engineering, Daejeon/Chungnam(Korea)-Kyushu(Japan)
  • Place of Presentation: Hanbat National University, Daejeon, Korea
  • Year and Date: 2007-12-01
• [Presentation] 初代ラット肝細胞と肝非実質細胞とのコラーゲンゲル内およびスフェロイド共培養による肝機能発現 (2007)
  • Author(s): 掛谷泰雄、横沼徹、尾方良平、境慎司、井嶋博之、川上幸衛
  • Organizer: 第59回日本生物工学会大会
  • Place of Presentation: 広島大学、東広島市
  • Year and Date: 2007-09-25
• [Presentation] 初代ラット肝細胞のコラーゲンゲル内共培養系の構築とその肝機能及び組織学的評価 (2007)
  • Author(s): 掛谷泰雄、横沼徹、境慎司、井嶋博之、川上幸衛
  • Organizer: 化学工学会第39回秋季大会
  • Place of Presentation: 北海道大学、札幌
  • Year and Date: 2007-09-13
• [Presentation] 動物細胞の機能性組織培養技術の開発と代謝系臓器構築への展開 (2007)
  • Author(s): 井嶋博之
  • Organizer: 第44回化学関連支部合同九州大会
  • Place of Presentation: 北九州国際会議場、北九州市
  • Year and Date: 2007-07-07
• [Presentation] Expression of maintenance of liver specific function of primary rat hepatocytes co-cultured with hepatic non-parenchymal cells in collagen gel (2007)
  • Author(s): Hiroyuki Ijima, Toru Yokonuma, Yasuo Kakeya, Shinji Sakai, Koei Kawakami
  • Organizer: TERMIS NA 2007 Conference and Exhibition
  • Place of Presentation: Toronto, ON (Westin Harbour Castle), Canada
  • Year and Date: 2007-06-14
• [Presentation] Expression of maintenance of liver specific function of primary rat hepatocytes co-cultured with hepatic non-parenchymal cells incollagen gel (2007)
  • Author(s): Hiroyuki Ijima, et. al.
  • Organizer: TERMIS NA 2007 Conference and Exhibition
  • Place of Presentation: Toronto, ON (Westin Harbour Castle), Canada
  • Year and Date: 2007-06-14
• [Presentation] Spheroid formation and expression of liver specific function of primary rat hepatocytes co-cultured with hepatic non-parenchymal cells (2007)
  • Author(s): Hiroyuki Ijima, Toru Yokonuma, Shinji Sakai, Koei Kawakami
  • Organizer: ASAIO's (American Society for Artificial Internal Organs) 53rd Annual Conference
  • Place of Presentation: Chicago, IL (Palmer House Hilton), USA
  • Year and Date: 2007-06-07
• [Presentation] Spheroid formation and expression of liver specific function of primary rat hepatocytes co-cultured with hepatic non-parenchymal cells (2007)
  • Author(s): Hiroyuki Ijima, et. al.
  • Organizer: ASAIO's(American Society for Artificial Internal Organs)53rd Annual Conference
  • Place of Presentation: Chicago, IL(Palmer House Hilton), USA
  • Year and Date: 2007-06-07
• [Presentation] 初代ラット肝細胞の薬物代謝酵素活性に及ぼす培養環境の影響 (2007)
  • Author(s): 掛谷泰雄、松尾健、境慎司、井嶋博之、川上幸衛
  • Organizer: 化学工学会第72年会
  • Place of Presentation: 京都大学
• [Presentation] 肝細胞と血管内皮細胞との共培養による肝機能発現の検討 (2006)
  • Author(s): 横沼徹, 境慎司, 井嶋博之, 川上幸衛
  • Organizer: 日本生物工学会九州支部鹿児島大会
  • Place of Presentation: 鹿児島大学
• [Presentation] 任意形状の血管様構造体の作製およびHep G2 との共培養 (2006)
  • Author(s): 武井孝行, 境 慎司, 井嶋博之, 川上幸衛
  • Organizer: 第58回日本生物工学会大会
  • Place of Presentation: 大阪大学