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ESTABLISHMENT OF FUNDAMENTAL STRATEGIES FOR SKELETAL MUSCLE TISSUE REGENERAIZON USING HEMATOPOIETIC CELLS FOR MUSCULAR DYSTROPHY DISEASE

Research Project

Project/Area Number 14370246
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HEIKE Toshio  KYOTO U., PEDIATRICS, ASSOCIATE PROFESSOR, 医学研究科, 助教授 (90190173)

Co-Investigator(Kenkyū-buntansha) ADACHI Soichi  KYOTO U., PEDIATRICS, ASSISTANT PROFESSOR, 医学研究科, 助手 (10273450)
YORIFUJI Tohru  KYOTO U., PRDIATRICS, LECTURER, 医学研究科, 講師 (60220779)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2003: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2002: ¥6,600,000 (Direct Cost: ¥6,600,000)
Keywordshematopoietic stem cell / skeletal muscle / plasticity / irradiation / c-kit / satellite cell / 筋ジストロフィー症 / 骨髄細胞 / 幹細胞 / GFP / single fiber culture / ラミニン
Research Abstract

Recently, the differentiation. into other lineages than hematopoietic origein was confirmed after bone marrow transplantation not only in mice but also in humans, including skeletal muscle tissue. This observation imply the following two possibilities; 1) the presence of pluripotent stem cells. in bone marrow, 2) the plasticity of bone marrow stem cells. Otherwise, the fusion of two kinds of cells with different characteristics was proposed to be the cause of this transdifferentiation. In the case of the transdifferentiation into skeletal muscle, the major contribution mechanism among these three possibilities is obscure. In this project, -we intended to analyze the mechanism four the transdifferentiation of bone, marrow cells into skeletal muscle tissue after the transplantation of bone marrow cells from GFP transgenic mice. into irradiated normal adult mice or W/W mice with c-kit mutation. In addition, in vitro system, we intended to establish, the cell line with the differentiation potential into skeletal muscle. First, after transplanting the KSL cells with GFP labeling, we could easily detect the skeletal muscle with y GFP expression. This GFP expression decreased gradually and faded out after 30 days. However, the culture of single muscle fiber from this transplanted mice revealed the expression with GFP expression, indicating the conversion into satellite veils with stem cell characteristics from transplanted KSL cells. On the other hand, we are now in the way to characterize the cell line with differentiation potential into skeletal muscle tissue.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Yasumi, T. et al.: "Differential requirement of the CD40-CD154 costimulatory pathway during T helper cell proming by CD8alpha+ and CD8alpha- murine dendritic cell subsets"J.Immunol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Umeda, K. et al.: "Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro"Development. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Xu, Y.et al.: "Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice"Arteriosclerosis, Thrombosis, and Vascular Biology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikomori, R. et al.: "X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development/or survival"Blood. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Heike T. et al.: "Stem cell plasticity in hematopoietic system"Int J Hematol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kambe N. et al.: "Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body"Blood. 103. 860-867 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsui, T. et al.: "Impaired neutraphil maturation in truncated G-CSF receptor-transgenic mice"Blood. 101. 2990-2996 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshimoto, M. et al.: "Direct visualization of transplanted hematopoietic cell reconstitution in intact mouse organs indicated the presence of a niche"Exp Hematol. 31. 733-740 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiramatsu, H. et al.: "Complete reconstitution of human lymphocytes drom cord blood CD34+ cells using the NOD/SCID/γ_c^<null> mice model"Blood. 102. 873-880 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Heike T., (in press), T.: "Ex vivo expansion of hematopoietic stem cells by cytokines."Biochim Biophys Acta. 1592. 312-313 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ito, M., Kobayashi, K., Suzue, K., Kawahata, M., Hioki, K., Ueyama, Y, Koyanagi, Y., Sugamura, K., Tsuji, K., Hiramatsu; H., Heike, T., Nakahata, T: "NOD/SCID gcnull mouse: An excellent recipient mouse model for engraftment of human cells."Blood. 100. 3175-3182 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hiramatsu, H., Nishikomori, R., Heike, T., Ito, M., Kobayashi, K., Katamura, K., Nakahata, T.: "Complete reconstitution of human lymphocytes drom cord blood CD34+ cells using the NOD/SCID/γc^<null> mice model"Blood. 102. 873-880 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yoshimoto, M., Shinohara, T., Heike, T., Shiota, M., Kanatsu-Shiriohara, M., Nakahata, T.: "Direct visualization of transplanted, hematopoietic cell reconstitution in intact mouse organs indicated the presence of a niche"Exp Hematol. 31. 733-740 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Mitsui, T.watanabe, S., Taniguchim Y., Hanada, S., Ebihara, Y., Sato, T., Heike, T., Mitsuyama, M.., Nakahata, T., Tsuji, K.: "Impaired neutrophil maturation in truncated G-CSF receptor-transgenic mice"Blood. 101. 2990-2995 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kambe N, Hiramatsu H, Shimonaka M, Fujino H, Nishikomori R, Heike T, Ito M, Kobayashi K, Ueyama Y, Matsuyoshi N, Miyachi Y, Nakahata T: "Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body."Blood. 103. 860-867 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Heike T, Nakahata T: "Stem cell plasticity in hematopoietic system"Int J Hematol. 79. 7-14 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikomori, R., Akutagawa, H., Maruyama, K., Nakata-Hizume, M., Ohmori, K., Mizuno, A., Yasumi, T., Kus unoki, T., Hei ke, T., Nakahata, T.: "X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development/or survival"Blood. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Xu, Y., Arai, H., Sario, H., Murayama, T., Yoshimoto, M., Heike, T., Nakahata, T., Nishikawa, S., Kita, T., Yokode, M.: "Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice"Arteriosclerosis, Thrombosis, and Vascular Biology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Umeda, K., Heike, T., Yoshimoto, M., Shiota, M., Suemori, H., Luo, H.Y, Ch.ui, D.H.K., Torii, R., Shibuya, M., Nakatsuji, N., Nakahata, T.: "Development of primitive and definitive hematopoiesis from nonhuman primate embryonic ste cells in vitro"Development. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasumi T, Katamura K, Yoshioka T, Meguro TA, Nishikomori R, Heike T, Inobe M, Kon S, Uede T, Nakahata T.: "Differential requirement of the CD40-CD154 costimulatory pathway during T helper cell proming by CD8alpha+ and CD8alpha-murine dendritic cell subsets"J.Immunol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yasumi, T., et al.: "Differential requirement for the CD40-CD154 costimulatory pathway during T helper cell proming by CD8alpha+ and CD8alpha- murine dendritic cell subsets"J.Immunol.. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Umeda, K., et al.: "Development of primitive and definitive hematopoiesis from nonhuman primate embryonic stem cells in vitro"Development. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Xu, Y., et al.: "Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice"Arteriosclerosis, Thrombosis, and Vascular Biology. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishikomori, R., et al.: "X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival"Blood. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Heike T., et al.: "Stem cell plasticity in hematopoietic system"Int J Hematol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kambe N., et al.: "Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body"Blood. 103. 860-867 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mitsui, T., et al.: "Impaired neutrophil maturation in truncated G-CSF receptor-transgenic mice"Blood. 101. 2990-2996 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshimoto, M., et al.: "Direct visualization of transplanted hematopoietic cell reconstitution in intact mouse organs indicated the presence of a niche"Exp Hematol. 31. 733-740 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiramatsu, H., et al.: "Complete reconstitution of human lymphocytes drom cord blood CD34+ cells using the NOD/SCID/γ_c^<null> mice model"Blood. 102. 873-880 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Heike T et al.: "Ex vivo expansion of hematopoietic stem cells by cytokines"Biochemica et Biophysica Acta. 199 2. 313-321 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito M et al.: "NOD/SCID/γ_c^<nell> mouse: an excellent recipient mouse model for engraftment of human cells"Blood. 100. 3175-3182 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiramatsu H et al.: "Complete reconstitution of human lymphocytes from cord blood CD34^+ cells using the NOD/SCID/γ_c^<nell> mice model"Blood. (in press).

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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