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Development of the device for ex vivo expansion of cord blood stem cells and its clinical application

Research Project

Project/Area Number 11794036
Research Category

Grant-in-Aid for University and Society Collaboration

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionTokai University

Principal Investigator

HOTTA Tomomitsu  Tokai University, School of Medicine, Professor, 医学部, 教授 (70173606)

Co-Investigator(Kenkyū-buntansha) TSUJI Takashi  JT pharmaceutical co., Chief researcher, 主任研究員 (50339131)
KATO Shunichi  Tokai University, School of Medicine, Associate Professor, 医学部, 助教授 (70096212)
ANDO Kiyoshi  Tokai University, School of Medicine, Assistant Professor, 医学部, 講師 (70176014)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2001: ¥13,000,000 (Direct Cost: ¥13,000,000)
KeywordsCord blood / ex vivo expansion / stromal cell / hematopoietic stem cell / CD34+cell / 造血幹細胞移植 / マウス骨髄ストローマ細胞株 / 膜分離型共培養系 / サイトカイン / 臍帯血、 / 造血幹細胞、 / 体外増幅、 / 造血幹細胞移植、 / 膜分離型共培養系、
Research Abstract

Recently, cord blood has been calling attention as a third source for supplying hematopoietic stem cells, next to bone marrow and peripheral blood. However, the biggest problem with cord blood is its limitation : the amount of hematopoietic stem cells contained, which restricts the administration of cord blood to adults. We developed a unique system for culture in which cord blood and stromal cells are separated by membrane, but still keep contact through pores with 0.45 micrometer. We were able to expand cord blood stem cells with this system in experiments. For the clinical application, we have to attain 1) control of the contamination of xenogeneic proteins and micro-organisms derived from murine stromal cell line, 2) sacale up the culture system, and 3) evaluation of the engraftment and long-term sustain of hematopoiesis. For these purposes we ordered the bioventure company, Bioreliance Co., to check the contamination of xenogeneic proteins and micro-organism in the reference of the guideline from FDA and confirmed the murine stromal cell line, HESS-5, was free from xenogeneic micro-organism. We also developed the large scale culture system by using membrane of 100 cm2. We evaluated the expansion of SRC by using of quantitative SRC assay, and confirmed more than 10 times expansion of SRC within 5 days of culture. We started clinical protocol after the disussion in IRB.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (50 results)

All Other

All Publications (50 results)

  • [Publications] 堀田知光: "再生移行学のための細胞工学 造血幹細胞のたいがい増幅とその応用"学術月報. 52・12. 1256-1261 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Nakamura et al.: "Clonality analysis of granulocytes and T lymphocytes in health females by the PCR-based HUMARA method"International Journal of HEMATOLOGY. 69. 237-243 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Nakamura et al.: "Ex Vivo generation of CD34^+ Cells From CD34^-Hematopoietic Cells"Blood. 94・12. 4053-4059 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H Kawada et al.: "Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system"EXPERIMENTAL HEMATOLOGY. 27. 904-915 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安藤 潔: "造血幹細胞体外増幅の臨床応用"医学のあゆみ. 190・5. 568-573 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 堀田知光: "血液(臍帯血幹細胞の体外増幅)"Pharma Medica. 18・1. 30-39 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K Ando, T Hotta et al.: "Extensive generation of human CD34^+ hematopoietic stem cells from CD34(-)Lin(-)cells in vitro"Experimental Hematology. 28. 690-699 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Nakamura, T Hotta et al.: "Effective enrichment of the precursor populations of human CD34+ hematopoietic cells by newly developed filter system"British Journal of Hematology. 108. 801-804 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Shimakura, T Hotta et al.: "Murine stromal cells line HESS-5 maintains reconstituting ability of ex vivo-generated hematopoietic stein cells from human bone marrow and cytokine-mobilized peripheral blood"Stem Cells. 18. 183-189 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M Hagihara, Ando K et al.: "The efficient generation of CD83 positive immunocompetent dendritic cells from CD14 positive acute myelmoncytic or monocytic leukemia cells in vitro"Leukemia Research. (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Yu, M Hagihara, K Ando, T Hotta et al.: "Enhancement of human cord blood CD34^+ cells-derived natural killer cell cytotoxicity by dendritic cells"Journal of Immunology. 166. 1590-1600 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M Oki, K Ando, T Hotta et al.: "Efficient Lentivviral Transduction into Human Cord Blood CD34^+ Cells and Differ entiation into Dendritic Cells"Experimantal Hematology. 29. 1210-1217 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S Kato, K Ando, T Hotta et al.: "Absence of CD34^-Hematopoietic Precursor Population in the Recipients of CD34^+ Stem Cell Transplantation"Bone Marrow Transplant. 28. 587-595 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T Sato, K Ando, T Hotta et al.: "Acute lethal injury of lung and liver in mice transplanted with ex vivo expaned CTLs"Cell Transplantation. 10. 409-412 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H Kawada, K Ando, T Hotta et al.: "Hematopoietic progenitors and stem cells in skeletal muscule"Tissue Engineering for Therapeutic Use. 6. 51-56 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ando K: "Human CD34-Hematopoietic Stem Cells : Basic Aspects and Clinical Significance"International Journal Hematology. (In press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T Hotta: "Cell biology for regenerative medicine. Ex vivo expansion of hematopoietic stem cell and its application"Gakujyutubeppou. 52・12. 1256-1261 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Nakamura et al.: "Clonality analysis of granulocytes and T lymphocytes in health females by the PCR-based HUMARA method"International Journal of HEMATOLOGY. 69. 237-243 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Nakamura et al.: "Ex Vivo generation of CD34^+ Cells From CD34^- Hematopoietic Cells"Blood.. 94・12. 4053-4059 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H Kawada et al.: "Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system"EXPERIMENTAL HEMATOLOGY. 27. 904-915 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K Ando: "Clinical application of ex vivo expansion of hematopoietic stem cell"Igakunoayumi. 190・5. 568-573 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T Hotta: "Ex vivo expansion of cord blood stem cell"Pharma Medica. 18・1. 30-39 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K Ando, T Hotta et al.: "Extensive generation of human CD34^+ hematopoietic stem cells fromCD34(-)Lin(-)cells in vitro"Experimental Hematology. 28. 690-699 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Nakamura, T Hotta et al.: "Effective enrichment of the precursor populations of human CD34+ hematopoietic cells by newly developed filter system"British Journal of Hematology. 108. 801-804 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Shimakura, T Hotta et al.: "Murine stromal cells line. HESS-5 maintains reconstituting ability of ex vivo-generated hematopoietic stem cells from human bone marrow and cytokine-mobilized peripheral blood"Stem Cells. 18. 183-189 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M Hagihara, Ando K et al.: "The efficient generation of CD83 positive immunocompetent dendritic cells from CD14 positive acute myelomonocytic or monocytic leukemia cells in vitro"Leukemia Research. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Y Yu, M Hagihara, K Ando, T hotta et al.: "Enhancement of human cord blood CD34^+ cells-derived natural Killer cell cytotoxicity by dendritic cells"Journal of Immunology. 166. 1590-1600 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M Oki, K Ando, T Hotta et al.: "Efficient Lentivviral Transduction into Human Cord Blood CD34^+ Cells and Differ entiation into Dendritic Cells"Experimantal Hematology. 29. 1210-1217 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] S Kato, K Ando, T Hotta et al.: "Absence of CD34^- Hematopoietic Precursor Population in the Recipients of CD34^+ Stem Cell Transplantation"Bone Marrow Transplant. 28. 587-595 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T Sato, K Ando, T Hotta et al.: "Acute lethal injury of lung and liver in mice transplanted with ex vivo expaned CTLs"Cell Transplantation. 10. 409-412 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H Kawada, K Ando, T Hotta et al.: "Hematopoietic progenitors and stem cells in skeletal muscule"Tissue Engineering for Therapeutic Use. 6. 51-56 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ando K: "Human CD34- Hematopoietic Stem Cells : Basic Aspects and Clinical Significance"International Journal Hematology. In press. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ando K.: "Human CD34- Hematopoietic Stem Cells : Basic Aspects and Clinical Significance"International Journal of Hematology. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Oki M, Ando K, Hotta T, et al.: "Efficient Lentiviral Transduction into Human Cord Blood CD34+ Cells and Differentiation into Dendritic Cells"Experimental Hematology. 29. 1210-1217 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato S, Ando K, Hotta T, et al.: "Absence of CD34- Hematopoietic Precursor Population in the Recipients of CD34+ Stem Cell Transplantation"Bone Marrow Transplant. 28. 587-595 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yu Y, Hagihara M, Ando K, Hotta T, et al.: "Enhancement of human cor d blood CD34+ cell-derived natural killer cell cytotoxicity by dendritic cells"Journal of Immunology. 166. 1590-1600 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawada H, Ando K, Hotta T, et al.: "Hematopoietic progenitors and stem cells in skeletal muscle"Tissue Engineering for Therapeutic Use. 6. 51-56 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sato T, Ando K, Hotta T, et al.: "Acute lethal injury of lung and liver in mice transplanted with ex vivo expanded CTLs"Cell Transplantation. 10. 0409-412 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nakamura Y,Hotta T, et al.: "Ex vivo generation of CD34 positive cells from CD34 negative hematopoietic cells SRC derived from CD34(-)Lin(-)cells."Blood. 94. 4053-4059 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ando K,Hotta T, et al.: "Extensive generation of human CD34+ hematopoietic stem cells from CD34(-)Lin(-)cells in vitro."Experimental Hematology. 28. 690-699 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakamura Y,Hotta T, et al.: "Effective enrichment of the precursor populations of human CD34+ hematopoietic cells by newly developed filter system."British Jornal of Hematology. 108. 801-804 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimakura Y,Hotta Y, et al.: "Murine stromal cell line HESS-5 maintains reconstituting ability of ex vivo-generated hematopoietic stem cells from human bone marrow and cytokine-mobilized peripheral blood."Stem cells. 18. 183-189 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hagihara M,Ando K, et al.: "The efficient generation of CD83 positive immunocompetent dendritic cells from CD14 positive acute myelomonocytic or monocytic leukemia cells in vitro. "Leukemia Research. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yin Y,Hagihara M,Ando K, et al.: "Enhancement of human cord blood CD34+ cell-derived natural killer cell cvtotoxicity by dendric cells."Jornal of Immunology. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 堀田知光: "再生医工学のための細胞工学-造血幹細胞の体外増幅とその応用-"学術月報. 52・12. 1256-1261 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 堀田知光: "血液(臍帯血幹細胞の体外増幅)"PharmaMedia. 18・1. 31-39 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yousuke Nakahara et al.: "Clonality analysis of granulocytes and T lymphocytes in healthy females by the PCR-based HUMARA method"International Journal of HEMATOLOGY. 69. 237-243 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yousuke Nakahara et al.: "Ex Vivo Generation of CD34+ Cells From CD34- Hematopoietic Cells"Blood. 94・12. 4053-4059 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiroshi Kawada et al.: "Rapid ex vivo expansion of human umbilical cord hematopoietic progenitors using a novel culture system"EXPERIMENTAL HEMATOLOGY. 27. 904-915 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 安藤 潔: "造血幹細胞体外増幅の臨床応用"医学のあゆみ. 190・5. 568-573 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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