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2005 Fiscal Year Final Research Report Summary

Basic study on cartilage, bone and tendon tissue engineering by using physical factors

Research Project

Project/Area Number 15390539
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionSaitama Medical School

Principal Investigator

NAKATSUKA Takashi  Saitama Medical School, Plastic Surgery, Professor, 医学部, 教授 (80198134)

Co-Investigator(Kenkyū-buntansha) ICHIOKA Shigeru  Saitama Medical School, Plastic Surgery, Associate Professor, 医学部, 助教授 (60306272)
TOKIOKA Kazuyuki  Saitama Medical School, Plastic Surgery, Lecturer, 医学部, 講師 (70332616)
TAKATO Tsuyoshi  The University of Tokyo Hospital, Oral and Maxillofacial Surgery, Professor, 医学部, 教授 (90171454)
NAKAMURA Kozo  The University of Tokyo Hospital, Orthopedic Surgery, Professor, 医学部, 教授 (60126133)
HOSHI Kazuto  The University of Tokyo Hospital, Contribute lectures staff (associate professor), 医学部, 助教授 (30344451)
Project Period (FY) 2003 – 2005
KeywordsRegenerative Medicine / Physical factor / Scaffold / Differentiation / Proliferation
Research Abstract

A social concern has risen to the maintenance of quality of life (QOL). Aiming at the maintenance of QOL by making tissue engineered bone, cartilage and tendon, we tried to use the characteristics of such tissues [i.e. ; they sensitively react to physical factors such as a mechanical stress, a magnetic stimulation or etc]. First, the cell proliferation and the differentiation condition were optimized. To prepare a mesenchymal cell proliferation medium that does not contain fetal bovine serum (FBS), and that provides more than a 1000-fold increase in cell numbers within approximately a month, we investigated the combinational effects of 12 factors on the proliferation of human cells by analysis of variance in fractional factorial design. As a result, FGF-2, dexamethasone, insulin, and IGF-I possessed promotional effects on proliferation on chondrocytes, while the combination of FGF-2 with insulin or IGF-I synergistically enhanced the proliferation. Thus we concluded that such a combination of FGF-2 with insulin or IGF-I may be useful for promotion of auricular chondrocyte proliferation in a clinical application for cartilage regeneration. Next we discovered that the combination of BMP-2, insulin, and thyroid hormone (BIT) is suitable for resolving the problem of de-differentiation of the chondrocyte caused along with the long time cell culture. Then, we studied the characteristics of some hydrogels expected to be used in clinical application by investigating their effects on cell proliferation or differentiation. (228 words)

  • Research Products

    (62 results)

All 2006 2005 2004 2003 Other

All Journal Article (54 results) Book (5 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials.2006

    • Author(s)
      Yamaoka, H., Asato, H., Ogasawara, T., Nishizawa, S., Takahashi, T., Nakatsuka, T., Koshima, I., Nakamura, K., Kawaguchi, H., Chung, U-I, Takato, T., Hoshi K.
    • Journal Title

      J Biomed Mater Res (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Total reconstruction of the upper lip after resection of a malignant melanoma.2005

    • Author(s)
      Eguchi T. et al.
    • Journal Title

      Scand J Plast Reconstr Surg Hand Surg. 39

      Pages: 45-47

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The positive experience of using a growtn factor product on deep wounds with exposed bone.2005

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      J Wound Care 14

      Pages: 105-109.

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Analysis of iscnemia-reperfusion injury in a microcircuiatory model of pressure ulcers.2005

    • Author(s)
      Tsuji S et al..
    • Journal Title

      Wound Repair Regen

      Pages: 209-215

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Secondary reconstruction of failed esophageal reconstruction.2005

    • Author(s)
      Okazaki M. et al.
    • Journal Title

      Ann Plast Surg 54

      Pages: 530-537

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Benefits of surgical reconstruction in pressure ulcers with a non-advancing edge and scar formation.2005

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      J Wound Care 14

      Pages: 301-305

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Two cases of Tessier no.4 cleft with anophthalmia.2005

    • Author(s)
      Tokioka K. et al.
    • Journal Title

      Cleft Palate Craniofac J 42

      Pages: 448-452

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Choice of osseous and osteocutaneous flaps for mandibular reconstruction.2005

    • Author(s)
      Takushima A. et al.
    • Journal Title

      Int J Clin Oncol 10

      Pages: 234-242

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocvtes.2005

    • Author(s)
      Takahashi T. et al.
    • Journal Title

      Cell Transplant 14

      Pages: 683-693

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Inhibition of Cdk6 expression through p38 MAP kinase is involved in differentiation of mouse prechondrocyte ATDC5.2005

    • Author(s)
      Moro T.et al.
    • Journal Title

      J Cell Physiol 204

      Pages: 927-933

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Osteoarthritis development in novel experimental mouse models induced by knee joint instability.2005

    • Author(s)
      Kamekura s. et al.
    • Journal Title

      Osteoarthritis Cartilage 13

      Pages: 632-641

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The canonical Wnt signaling pathway promotes chondrocvte differentiation in a Sox9-ceDendent manner.2005

    • Author(s)
      Yano, F. et al.
    • Journal Title

      Biocbem Biophys Res Commun 333

      Pages: 1300-1308

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Total reconstruction of the upper lip after resection of a malignant melanoma.2005

    • Author(s)
      Eguchi T., Nakatsuka T., Mori Y., Takato T.
    • Journal Title

      Scand J Plast Reconstr Surg Hand, Surg. 39

      Pages: 45-47

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The positive experience of using a growth factor product on deep wounds with exposed bone.2005

    • Author(s)
      Ichioka S., Ohura N., Nakatsuka T.
    • Journal Title

      J Wound Care 14

      Pages: 105-109

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers.2005

    • Author(s)
      Tsuji S., Ichioka S., Sekiya N., Nakatsuka T.
    • Journal Title

      Wound Repair Regen 13

      Pages: 209-215

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Secondary reconstruction of failed esophageal reconstruction.2005

    • Author(s)
      Okazaki M., Asato H., Takushima A., Nakatsuka T., Harii K.
    • Journal Title

      Ann Plast Surg 54

      Pages: 530-537

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Benefits of surgical reconstruction in pressure ulcers with a non-advancing edge and scar formation.2005

    • Author(s)
      Ichioka S., Ohura N., Nakatsuka T.
    • Journal Title

      J Wound Care 14

      Pages: 301-305

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Two cases of Tessier no.4 cleft with anophthalmia.2005

    • Author(s)
      Tokioka K., Nakatsuka T., Park S., Okouchi M., Aiba E.
    • Journal Title

      Cleft Palate Craniofac J 42

      Pages: 448-452

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Choice of osseous and osteocutaneous flaps for mandibular reconstruction.2005

    • Author(s)
      Takushima A., Harii K., Asato H., Momosawa A., Okazaki M., Nakatsuka T.
    • Journal Title

      Int J Clin Oncol 10

      Pages: 234-242

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synergistic effects of FGF-2 with insulin or IGF-I on the proliferation of human auricular chondrocytes.2005

    • Author(s)
      Takahashi, T., Ogasawara, T., Kishimoto, J., Liu, G., Asato, H., Nakatsuka, T., Uchinuma, E., Nakamura, K., Kawaguchi, H., Takato, T., Hoshi, K.
    • Journal Title

      Cell Transplant 14

      Pages: 683-693

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of Cdk6 expression through p38 MAP kinase is involved in differentiation of mouse prechondrocyte ATDC5.2005

    • Author(s)
      Moro, T., Ogasawara, T., Chikura, H., Ikeda, T., Ogata, N., Maruyama, Z., Komori, T., Hoshi, K., Chung, U.I., Nakamura, K., Okayama, H., Kawaguchi, H.
    • Journal Title

      J Cell Physiol 204

      Pages: 927-933

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Osteoarthritis development in novel experimental mouse models induced by knee joint instability.2005

    • Author(s)
      Kamekura, S., Hoshi, K., Shimoaka, T., Chung, U., Chikuda, H., Yamada, T., Uchida, M., Ogata, N., Seichi, A., Nakamura, K., et al.
    • Journal Title

      Osteoarthritis Cartilage 13

      Pages: 632-641

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The canonical Wnt signaling pathway promotes chondrocyte differentiation in a Sox9-dependent manner.2005

    • Author(s)
      Yano, F., Kugimiya, F., Ohba, S., Ikeda, T., Chikuda, H., Ogasawara, T., Ogata, N., Takato, T., Nakamura, K., Kawaguchi, H., Chung, U.I.
    • Journal Title

      Biochem Biophys Res Commun 333

      Pages: 1300-1308

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Bone marrow cell implantation improves flap viability after ischemia-reperfusion injury.2004

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      Ann Plast Surg 52

      Pages: 414-418

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Triple coverage of ischial ulcers with adipofascial turnover and fasciocutaneous flaps.2004

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      Plast Reconstr Surg 114

      Pages: 901-905

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Distal perforator based fasciocutaneous V-Y flap for treatment of sacral pressure ulcers.2004

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      Plast Reconstr Surg 114

      Pages: 906-909

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A symmetrical dorsal island double flap in the mouse. Eur J Plast Surg 27 : 29-32.2004

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      Eur J Plast Surg 27

      Pages: 29-32

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.2004

    • Author(s)
      Hoshi K. et al.
    • Journal Title

      J Bone Miner Res 19

      Pages: 214-223

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Osteoclast differentiation by RANKL requires NF-_kB-mediated downregulation of cyclin-dependent kinase 6 (Cdk6).2004

    • Author(s)
      Ogasawara T. et al.
    • Journal Title

      J Bone Miner Res 19

      Pages: 1128-1136

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6.2004

    • Author(s)
      Ogasawara T. et al.
    • Journal Title

      Mol Cell Biol 24

      Pages: 1650-6568

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.2004

    • Author(s)
      Chikuda H. et al.
    • Journal Title

      Genes Dev 18

      Pages: 2418-2429

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The combination of SOX5, SOX6, and SOX9(the SOX trio)provides signals sufficient for induction of permanent cartilage.2004

    • Author(s)
      Ikeda T. et al.
    • Journal Title

      Arthritis Rheum 50(11)

      Pages: 3561-3573

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Bone marrow cell implantation improves flap viability after ischemia-reperfusion injury.2004

    • Author(s)
      Ichioka S., Kudo S., Shibata M., Ando J., Sekiya N., Nakatsuka T.
    • Journal Title

      Ann Plast Surg 52

      Pages: 414-418

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Triple coverage of ischial ulcers with adipofascial turnover and fasciocutaneous flaps.2004

    • Author(s)
      Ichioka S., Okabe K., Tsuji S., Ohura N., Nakatsuka T.
    • Journal Title

      Plast Reconstr Surg 114

      Pages: 901-905

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Distal perforator based fasciocutaneous V-Y flap for treatment of sacral pressure ulcers.2004

    • Author(s)
      Ichioka S., Okabe K., Tsuji S., Ohura N., Nakatsuka T.
    • Journal Title

      Plast Reconstr Surg 114

      Pages: 906-909

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A symmetrical dorsal island double flap in the mouse.2004

    • Author(s)
      Ichioka S., Kudoh S., Tokioka K.
    • Journal Title

      Eur J Plast Surg 27

      Pages: 29-32

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.2004

    • Author(s)
      Hoshi, K., Ogata, N., Shimoaka, T., Terauchi, Y., Kadowaki, T., Kenmotsu, S., Chung, U.I., Ozawa, H., Nakamura, K., Kawaguchi, H.
    • Journal Title

      J Bone Miner Res 19

      Pages: 214-223

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Osteoclast differentiation by RANKL requires NF-kappaB-mediated downregulation of cyclin-dependent kinase 6 (Cdk6).2004

    • Author(s)
      Ogasawara, T., Katagiri, M., Yamamoto, A., Hoshi, K., Takato, T., Nakamura, K., Tanaka, S., Okayama, H., Kawaguchi, H.
    • Journal Title

      J Bone Miner Res 19

      Pages: 1128-1136

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Bone morphogenetic protein 2-induced osteoblast differentiation requires Smad-mediated down-regulation of Cdk6.2004

    • Author(s)
      Ogasawara, T., Kawaguchi, H., Jinno, S., Hoshi, K., Itaka, K., Takato, T., Nakamura, K., Okayama, H.
    • Journal Title

      Mol Cell Biol 24

      Pages: 6560-6568

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cyclic GMP-dependent protein kinase II is a molecular switch from proliferation to hypertrophic differentiation of chondrocytes.2004

    • Author(s)
      Chikuda, H., Kugimiya, F., Hoshi, K., Ikeda, T., Ogasawara, T., Shimoaka, T., Kawano, H., Kamekura, S., Tsuchida, A., Yokoi, N., Nakamura, K., Komeda, K., Chung, U.I., Kawaguchi, H.
    • Journal Title

      Genes Dev 18

      Pages: 2418-2429

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The combination of SOX5, SOX6, and SOX9 (the SOX trio) provides signals sufficient for induction of permanent cartilage.2004

    • Author(s)
      Ikeda T., Kamekura S., Mabuchi A., Kou I., Seki S., Takato T., Nakamura K., Kawaguchi H., Ikegawa S., Chung UI.
    • Journal Title

      Arthritis Rheum 50(11)

      Pages: 3561-3573

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analytic review of 2372 free flap transfers for head and neck reconstruction following cancer resection.2003

    • Author(s)
      Nakatsuka T. et al.
    • Journal Title

      J Reconstr Microsurg 19

      Pages: 363-368

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Analysis of the relations between the shape of the reconstructed ongue and postoperative functions after subtotal or total glossectomy.2003

    • Author(s)
      Kimata Y. et al.
    • Journal Title

      Laryngoscope 113

      Pages: 905-909

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Skin temperature changes induced by strong static magnetic field exposure.2003

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      Bioelectromagnetics 24

      Pages: 380-386

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Regenerative surgery for sacral pressure ulcers using collagen matrix substitute dermis (artificial dermis ).2003

    • Author(s)
      Ichioka S. et al.
    • Journal Title

      Ann Plast Surg 51

      Pages: 383-389

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Global analysis of shear stress-responsive genes in vascular endothelial cells.2003

    • Author(s)
      Ohura N. et al.
    • Journal Title

      J Atheroscler Thromb 10

      Pages: 304-313

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cystatin 10, a novel chondrocyte-specific protein, may promote thelast steps of the chondrocyte differentiation pathway.2003

    • Author(s)
      Koshizuka Y. et al.
    • Journal Title

      J Biol Chem 278

      Pages: 48259-48266

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Analytic review of 2372 free flap transfers for head and neck reconstruction following cancer resection.2003

    • Author(s)
      Nakatsuka T., Harii K., Asato H., Takushima A., Ebihara S., Kimata Y., Yamada A., Ueda K., Ichioka S.
    • Journal Title

      J Reconstr Microsurg 19

      Pages: 363-368

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Analysis of the relations between the shape of the reconstructed tongue and postoperative functions after subtotal or total glossectomy.2003

    • Author(s)
      Kimata Y, Sakuraba M, Hishinuma S, Ebihara S, Hayashi R, Asakage T, Nakatsuka T, Harii K.
    • Journal Title

      Laryngoscope 113

      Pages: 905-909

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Skin temperature changes induced by strong static magnetic field exposure.2003

    • Author(s)
      Ichioka S., Minegishi M., Iwasaka M., Shibata M., Nakatsuka T., Ando J., Ueno S.
    • Journal Title

      Bioelectromagnetics 24

      Pages: 380-386

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Regenerative surgery for sacral pressure ulcers using collagen matrix substitute dermis (artificial dermis).2003

    • Author(s)
      Ichioka S., Ohura N., Sekiya N., Shibata M., Nakatsuka T.
    • Journal Title

      Ann Plast Surg 51

      Pages: 383-389

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Global analysis of shear stress-responsive genes in vascular endothelial cells.2003

    • Author(s)
      Ohura N., Yamamoto K., Ichioka S., Sokabe T., Nakatsuka H., Baba A., Shibata M., Nakatsuka T., Harii K., Wada Y., Kohro T., Kodama T., Ando J.
    • Journal Title

      J Atheroscler Thromb 10

      Pages: 304-313

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cystatin 10, a novel chondrocyte-specific protein, may promote the last steps of the chondrocyte differentiation pathway.2003

    • Author(s)
      Koshizuka, Y., Yamada, T., Hoshi, K., Ogasawara, T., Chung, U.I., Kawano, H., Nakamura, Y., Nakamura, K., Ikegawa, S., Kawaguchi, H.
    • Journal Title

      J Biol Chem 278

      Pages: 48259-48266

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cartilage tissue engineering using human auricular chondrocvtes embedded in different hydrogel materials.

    • Author(s)
      Yamaoka H. et al.
    • Journal Title

      J Biomed Mater Res (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 顕微鏡下の肝動脈再建「肝臓外科の要点と盲点」第2版2006

    • Author(s)
      中塚貴志
    • Total Pages
      472
    • Publisher
      文光堂
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 新家庭の医学2005

    • Author(s)
      中塚貴志 ほか
    • Total Pages
      1560
    • Publisher
      時事通信社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] TEXT 標準形成外科2004

    • Author(s)
      中塚貴志
    • Total Pages
      422
    • Publisher
      南山堂
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 血管腫・血管奇形の診断と治療のストラテジー2004

    • Author(s)
      時岡一幸 ほか
    • Total Pages
      165
    • Publisher
      先端医学社
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 新臨床耳鼻咽喉科学 5巻-基本手術手技2003

    • Author(s)
      中塚貴志
    • Total Pages
      304
    • Publisher
      中外医学社
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 脱分化型軟骨細胞の軟骨細胞への再分化用培地2005

    • Inventor(s)
      星 ほか
    • Industrial Property Rights Holder
      星 ほか
    • Industrial Property Number
      PCT/JP/2005/015280
    • Filing Date
      2005-08-23
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 細胞培養用中空糸モジールおよび細胞培養方法2005

    • Inventor(s)
      星 ほか
    • Industrial Property Rights Holder
      星 ほか
    • Industrial Property Number
      特願 2005-176438
    • Filing Date
      2005-06-16
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 脱分化型軟骨細胞の軟骨細胞への再分化培地2005

    • Inventor(s)
      星 ほか
    • Industrial Property Rights Holder
      星 ほか
    • Industrial Property Number
      PCT出願 PCT/JP2005-015280
    • Filing Date
      2005-08-23
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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