Generating transplantable artificial tissues composed of collagen fibrils and cells using a newly designed bioreactor

2009 Fiscal Year Final Research Report

• Project/Area Number: 19300174
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Kitasato University
• Principal Investigator: ADACHI Eijiro Kitasato University, 医療系研究科, 教授 (30110430)
• Co-Investigator(Kenkyū-buntansha): NISHIYAMA Toshio 東京農工大学, 農学部, 教授 (60372455) ; TAGAWA Yoh-Ichi 東京農工大学, 生命理工学研究科, 准教授 (70262079)
• Project Period (FY): 2007 – 2009
• Keywords: 高密度培養法 / コラーゲン / 人工皮膚 / 表皮細胞 / 人工血管 / 平滑筋細胞

Research Abstract

We have designed a new device to form artificial tissues from culture medium supplemented with collagen I and various cells less than 24 hours. Moreover, we stack up 3 different tissue layers in the same bioreactor by supplementing newly prepared culture medium containing various extracellular matrices, such as collagen and proteoglycans, and different types of cells. Embedded cells restore their specific functions of original tissues, i.e. up-regulation of smooth muscle type myosin the tissues. Using this technique, we can supply artificial tissues applicable to clinical use with relative ease.

Research Products

• [Journal Article] In vitro reprogramming of adult hepatocytes into insulin-producing cells without viral vectors. (2009)
  • Author(s): Motoyama, H., Ogawa, S., Kubo, A., Miwa, S., Nakayama, J., Tagawa, Y., Miyagawa, S.
  • Journal Title: Biochem. Biophys. Res. Commun. 385 Pages: 123-128
  • Peer Reviewed
• [Journal Article] Coenzyme Q(10) protects against oxidative stress-induced cell death and enhances the synthesis of basement membrane components in dermal and epidermal cells. (2009)
  • Author(s): Muta-Takada, K., Terada, T., Yamanishi, H., Ashida, Y., Inomata, S., Nishiyama, T., Amano, S.
  • Journal Title: Biofactors 35 Pages: 435-441
  • Peer Reviewed
• [Journal Article] Effects of vitamin C deficiency on the skin of the senescence marker protein-30 (SMP30) knockout mouse. Biochem. (2009)
  • Author(s): Arai, K.Y., Sato, Y., Kondo, Y., Kudo, C., Tsuchiya, H., Nomura Y, Ishigami A, Nishiyama, T.
  • Journal Title: Biophys. Res. Commun. 385 Pages: 478-83
  • Peer Reviewed
• [Journal Article] Mucosal remodeling in long-standing ulcerative colitis with colorectal neoplasia: Significant alterations of NCAM+ or α-SMA+ subepithelial myofibroblasts and interstitial cells. (2009)
  • Author(s): Okayasu, I., Yoshida, T.., Mikami, T., Hana, K., Yokozawa, M., Araki, K, Mitsuhashi, J., Kikuchi, M., Adachi, E., Sada, M
  • Journal Title: Pathology International 59 Pages: 01-711
  • Peer Reviewed
• [Journal Article] Abnormal collagen deposition in fibromas from patient with juvenile hyaline fibromatosis. (2009)
  • Author(s): Tanaka, K., Ebihara, T., Kusubata, M., Adachi, E., Arai, M., Kawaguchi, N., Utsunomiya J., Miki, Y., Hiramoto, M., Shunji Hattori S., Irie, A.
  • Journal Title: J. Dermatol. Sci. 55 Pages: 197-200
  • Peer Reviewed
• [Journal Article] Mechanical strain increases expression of type XII collagen in murine osteoblastic MC3T3-E1 cells. (2008)
  • Author(s): Arai, K., Nagashima, Y., Takemoto T, Nishiyama T
  • Journal Title: Cell Struct. Funct. 33 Pages: 203-210
  • Peer Reviewed
• [Journal Article] Plasmin induces degradation and dysfunction of laminin 332 (laminin 5) and impaired assembly of basement membrane at the dermal-epidermal junction. (2008)
  • Author(s): Ogura, Y., Matsunaga, Y., Nishiyama, T., Amano, S.
  • Journal Title: Br. J. Dermatol. 159 Pages: 49-60
  • Peer Reviewed
• [Journal Article] Deficiency of tumour necrosis factor-alpha and interferon-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury. (2008)
  • Author(s): Murayama, H., Takahashi, M., Takamoto, M., Shiba, Y., Ise, H., Koyama, J., Tagawa, Y., Iwakura, Y., Ikeda, U.
  • Journal Title: Cardiovasc. Res. 80 Pages: 175-180
  • Peer Reviewed
• [Journal Article] Hepatoprotective effect of vitamin B12 on dimethylnitrosamine-induced liver injury. (2008)
  • Author(s): Isoda, K., Kagaya, N., Akamatsu, S., Hayashi, S., Tamesada, M., Watanabe, A., Kobayashi, M., Tagawa, Y., Kondoh, M., Kawase, M., Yagi, K.
  • Journal Title: Biol. Pharm. Bull 31 Pages: 309-311
  • Peer Reviewed
• [Journal Article] Keratinocyte differentiation and proliferation are regulated by adhesion to the three-dimensional meshwork structure of type IV collagen. (2008)
  • Author(s): Fujisaki, H., Adachi, E., Hattori, S.
  • Journal Title: Connective Tissue Research 49 Pages: 426-436
  • Peer Reviewed
• [Journal Article] Intercellular accumulation of type V collagen fibrils in accordance with cell aggregation. (2008)
  • Author(s): Kihara, T., Imamura, Y., Takemura, Y., Mizuno, K., Adachi, E., Hayashi, T.
  • Journal Title: J. Biochem. 144 Pages: 625-633
  • Peer Reviewed
• [Presentation] Effects of reconstituted type IV collagen aggregates on epidermal structure and function in human skin equivalents 34th Annual Meeting of the Japanese Society for Investigative Dermatology (2009)
  • Author(s): Hachiya Y, Ito K, Arai KY, Sasaki T, Adachi E, Hayashi T, Nishiyama T.
  • Organizer: Fukuoka
  • Place of Presentation: Japan
  • Year and Date: 20091204-20091206
• [Presentation] Characterization of HepG2 cells accumulated on collagen gels populated with fibroblasts as hepatic tissue substitutes (2009)
  • Author(s): Satoshi Hosoya, Miho Tamai, Hironobu Iwashiro, Shiro Kikuchi, Masaki Ueno, Toshihiro Akaike, Yoh-ichi Tagawa, Masahiko Watanabe, Eijiro Adachi
  • Organizer: Collagen Gordon Conference: List of Posters p. 1
  • Place of Presentation: New London, New Hampshire, Gordon Research Conference on Collagen
  • Year and Date: 20090719-20090724
• [Presentation] Substrsate recognition of collagen-binding domains derived from bacterial collagenases (2009)
  • Author(s): Osamu Matsushita, Nozomu Nishi, Takaki koide, ST Leena Philominathan, Joshua Sakon, Robert C Gensure, Hironobu Iwashiro, Eijiro Adachi
  • Organizer: 8th Pan-Pacific Connective Tissue Societies Symposium
  • Place of Presentation: Yokosuka (Japan)
  • Year and Date: 20090604-20090607
• [Remarks] 細胞組織再生医学ホームページ
  • URL: http://morpholab.ahs.kitasato-u.ac.jp/adachilabHP/indexaj.html
• [Remarks] mediconサーバー
  • URL: http://medicon.ahs.kitasato-u.ac.jp/
• [Patent(Industrial Property Rights)] 人工皮膚 (2010)
  • Inventor(s): 入山俊介、海塩健一、常長誠、猪股慎二、安達栄治郎
  • Industrial Property Rights Holder: 株式会社資生堂
  • Industrial Property Number: 特許・特願2010-048159
  • Filing Date: 2010-03-04
• [Patent(Industrial Property Rights)] 積層型高密度培養人工組織の製造方法及び積層型培養人工組織 (2009)
  • Inventor(s): 安達栄治郎、松下治、岩城啓修、細谷智、西望
  • Industrial Property Rights Holder: 学校法人北里研究所
  • Industrial Property Number: 特許・特願2010-048159
  • Filing Date: 2009-01-29
• [Patent(Industrial Property Rights)] コラーゲン特異的分子シャペロンHSP47の測定方法 (2008)
  • Inventor(s): 渡邊昌彦、安達栄治郎、永田和宏、菊池史郎、小野里航、平井和弥
  • Industrial Property Rights Holder: 学校法人北里学園
  • Industrial Property Number: 特許・特許公開2008-122276
  • Acquisition Date: 2008-05-29
• [Patent(Industrial Property Rights)] 高密度培養組織の製造方法及び高密度培養組織 (2005)
  • Inventor(s): 安達栄治郎、大橋しほ花、平井和弥
  • Industrial Property Rights Holder: 学校法人北里学園
  • Industrial Property Number: 特許・wo2006/088029
  • Acquisition Date: 2005-02-15