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Establishment of in utero cell iransplantation and fetal gene therapy model using non-human primate

Research Project

Project/Area Number 11357009
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Embryonic/Neonatal medicine
Research InstitutionUniv. of Tsukuba

Principal Investigator

NAKAUCHI Hiromitsu  Institute of Basic Medical Sciences, Univ of Tsukuba, Dept of Immunology, Professor, 基礎医学系, 教授 (40175485)

Co-Investigator(Kenkyū-buntansha) TERAO Keiji  Tsukuba Primate Center, Natl Inst of Infec Dis., Lab. Head, 筑波医学実験用霊長類センター, 室長
SHIBUYA Kazuko  Research Tenter for Allergy and Immunology (RCAI), Research Scientist, 免疫アレルギー科学総合研究センター・免疫素受容体研究チーム, 研究員 (00302406)
SHIBUYA Akira  Institute of Basic Medical Sciences, Univ of Tsukuba, Dept of Immunology, Associate Professor, 基礎医学系, 助教授 (80216027)
ONODERA Masahumi  Institute of Clinical Med., Univ of Tsukuba, Div of Hematology, Assistant Professor, 臨床医学系, 講師 (10334062)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥36,620,000 (Direct Cost: ¥33,500,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2001: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2000: ¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 1999: ¥12,700,000 (Direct Cost: ¥12,700,000)
Keywordsin utero transplantation / in utero gene therapy / hematopoietic stem cells / crab-eatingmonkey / retroviralvector / microchimerism / レトロウィルスベクター / 子宮内胎児細胞移植 / サル / 遺伝子導入 / 異種移植 / 免疫寛容
Research Abstract

We initially developed an in utero cell transplantation model using pregnant pigs. Transplantation of human CB cells into pig fetuses aged <52 days post coitus resulted in a good engraftment rate. Although most of them were micro-chimerism, in some cases, human hematopoietic cells including CD34+ HSPCs were detectable also by FACS in PB and BM. Based on this transplantation model, we attempted in utero cell transplantation into monkey fetus for 4 times. Cells transplanted were human cord blood CD34+ cells, human T cells, human leukemic cells, and GFP transduced-monkey cord blood T cells. The transplantation process itself went smoothly as in a pig model. However, despite successful in utero cell transplantation, chimerism by the human cells was low or hardly detectable in the new born. GFP protein that we used for marking donor cells may be either antigenic or toxic. We need to accumulate more data before the application of in utero cell/gene transfer in the clinical settings.

Report

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

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Tahara H.S, et al.: "Lentiviral Vector-Mediated Transduction of Murine CD34-Hematpoietic Stem Cells"Exp. Hematology.. 30巻. 11-17 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhou S., et al.: "The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinat of the side-population phenotype"Nat Med. 7巻. 1028-1034 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osada H, et al.: "Detection of fetal HPCs in maternal circulatioi after delivery"Transfusion.. 41巻. 499-503 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kaneko S, et al.: "Simplified Retroviral Vector GCsap with Murine Stem Cell Virus Long Terminal Repeat Allows High and Continued Expression of Enhanced Green Fluorescent Protein by Human Hematopoietic Progenitors Engrafted in Nonobese Diabetic/Severe Combined Immunodeficient Mice"Hum Gene Ther. 12巻. 35-44 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiromitsu Nakauchi, et al.: "Quantitative assessment of the stem cell self-renewal capacity"Ann N Y Acad Sci. 938巻. 18-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Iwama A, Osawa M, Hirasawa R, Uchiyama N, Kaneko S, Onodera M, Shibuya K, Shibuya A, Vinson C, Tenen DG, Nakauchi H.: "Reciprocal Roles for CCAAT/Enhancer Binding (C/EBP) and PU.1 Transcription Factors in Langerhans Ceil Commitment Protein."J Exp Med.. 195. 547-558 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sousuke Miyoshi, Tsutomu Motohashi, Yukio Nakamura, Mitsujiro Osawa, Takashi Hiroyama, Dong-Ku Kim, Yasuhito Tokumoto, Hiromitsu Nakauchi: "A transmembrane trap method for efficient cloning of genes encoding proteins possessing transmembrane domain."Biochem. Biophys. Res. Commu.. 289. 1192-8 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tahara-H. S, Sudo K., Ema R, Miyoshi H., Nakauchi H.: "Lentiviral Vector-Mediated Transduction of Murine CD34- Hematopoietic Stem Cells."Exp. Hematology. 30. 11-7 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Atsushi Suzuki, Yun-wen Zheng, Shin Kanako, Masafumi Onodera, Katashi Fukao, Hiromitsu Nakauchi, Hideki Taniguchi: "Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver"Journal of Cell Biology. 156. 173-84 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Zhou S, Schuelz JD. Bunting KD, Colapielro AM, Sampath J, Morris JJ, Lajutina 1, Grosveld OC, Osawa M, Nakauchi H, Sorremino BP: "The ABC Iransporter Bcrpl/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype"Nat Med. 7. 1028-34 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osada H, Doi S, FukushimaT, Nakauchi H, Seki K, Sekiya S: "Detection of fetal HPCs in maternal circulation after delivery"Transfusion. 41. 499-503 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiromitsu Nakauchi, Kazuhiro Sudo, Hideo Emar: "Quantitative assessment of the stem cell self-renewal capacity"Stem Cell III. Ann N Y Acad Sci. 938. 18-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Osada H, Doi S, Fukushima T, Nakauchi H, Seki K, Sekiya S: "Detection of fetal HPCs in maternal circulation after delivery"Transfusion. 41. 499-503 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kaneko S, Onodera M, Fujiki Y, Nagasawa T, Nakauchi H: "Osada H, Doi S, Fukushima T, Nakauchi H. Seki K and Sekiya S /Detection of fetal HPCs in maternal circulation after delivery. ' Kaneko S, Onodera M, Fujiki Y, Nagasawa T and Nakauchi H /Simplified Retroviral Vector Gcsap with Murine Stem Cell Virus Long Terminal Repeat Allows High and Continued Expression of Enhanced Green Fluorescent Protein by Human Hematopoietic Progenitors Engrafted in Nonobese Diabetic/Severe Combined Immunodeficient Mice."Hum Gene Ther. 12. 35-44 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Taniguchi H, Kondo R, Suzuki A, Zheng YW, Takada Y, Fukunaga K, Seino K, Yuzawa K, Otsuka M, Fukao K, Nakauchi H: "Clonoaenic colony-forming ability of flow cytometrically isolated hepatic progenitor cells in the murine fetal liver"Cell Transplant. 9. 697-700 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki A, Zheng Y, Kondo R, Kusakabe M, Takada Y, Fukao K, Nakauchi H, Taniguchi H: "Flow-Cytometric Separation and Enrichment of Hepatic Progenitor Cells in the Developing Mouse Liver"Hepatology. 32. 1230-1239 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hsu HC, Ema H, Osawa M, Nakamura Y, Suda T, Nakauchi H: "Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver"Blood. 96. 3757-3762 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sudo K, Ema H, Morita Y, Nakauchi H: "Aoe-associated characteristics of murine hematopoietic stem cells"J Exp Med. 192. 1273-80 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ema H, Takano H, Sudo K, Nakauchi H: "In Vitro Self-Renewal Division of Hematopoietic Stem Cells"J Exp Med. 192. 1281-1288 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hideo Ema, Hiromitsu Nakauchi: "Expanshion of hematopoietic stem cells in the developing liver of a mouse embryo"Blood. 95. 2284-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kaneta M, Osawa M, Sudo K, Nakauchi H: "Farr AG and Takahama Y A role for pref-1 and HES-1 in thymocyte development"J Immunol. 164. 256-64 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujiki Y, Onodera M, Yamaguehi T, Osawa M, Sudo K, Hamada H, Ema H, Shibuya A, Takiguchi M, Kubo T, Nakauchi H: "Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments"Exp Hematol. 28. 792-801 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroyama T, Iwama A, Morita Y, Nakamura Y, Shibuya A, Nakauchi H: "Molecular cloning and characterization of CRLM-2, a novel type I cytokine receptor preferentially expressed in hematopoietic cells"Biochem Biophys Res Commun. 272. 224-9 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mitsujiro Osawa^*, Sousuke Miyoshi^*, Neal G. Copeland, Debra J. Gilbert, Nancy A, Jenkins, Takashi Hiroyama, Tsutomu Motohashi, Yukio Nakamura, Atsushi Iwama, Hiromitsu Nakauchi, (*These two authors contributed equally to this work.): "Characterization of Murine lnterleukin-13 Receptor alpha 1 Gene"Immunogenetics. 51. 974-81 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakauchi H, Takano H, Ema H, Osawa M: "Further characterization of CD34-low/negative mouse hematopoietic stem cells"Ann N Y Acad. 872 (discussion 66-70). 57-66 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hideyuki Murata, Hiromitsu Nakauchi, Takayuki Sumida: "Microchimerism in Japanease women patients with systemic sclerosis"The Lancet. 354. 220 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Dong Ku Kim^*, Yutaka Fujiki^*, Takashi Fukushma, Hideo Ema, Akira Shibuya, Hiromitsu Nakauchi, (*These two authors contributed equally to this work.): "Comparison of Hematopoietic Activities of Human Bone Marrow and Umbilical Cord Blood CD34 Positive and Negative Cells"STEM CELLS. 17. 286-294 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tahara-H.S., et al.: "Lentiviral Vector-Mediated Transduction of Murine CD34-Hematopoietic Stem Cells"Exp. Hematology.. 30巻. 11-17 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Zhou S., et al.: "The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype"Nat Med. 7巻. 1028-1034 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Osada H., et al.: "Detection of fetal HPCs in maternal circulation after delivery"Transfusion.. 41巻. 499-503 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kaneko S., et al.: "Simplified Retroviral Vector GCSap with Murine Stem Cell Virus Long Terminal Repeat Allows High and Continued Expression of Enhanced Green Fluorescent Protein by Human Hematopoietic Progenitors Engrafted in Nonobese Diabetic/Severe Combined Immunodeficient Mice"Hum Gene Ther. 12巻. 35-44 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] <Hiromitsu Nakauchi>__-, at al.: "Quantitative assessment of the stem cell self-renewal capacity"Ann N Y Acad Sci. 938巻. 18-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kaneko S et al.: "Simplified Retroviral Vector GCsap with Murine Stem Cell Virus Long Terminal Repeat Allows High and Continued Expression of Enhanced Green Fluorescent Protein by Human Hematopoietic Progenitors Engrafted in Nonobese Diabetic/Severe Combined Immunodeficient Mice."Hum Gene Ther. Vol.12. 35-44 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hsu HC et al.: "Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver."Blood. Vol.96. 3757-3762 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sudo K et al.: "Age-associated characteristics of murine hematopoietic stem cells."J Exp Med. Vol.192. 1273-1280 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ema H et al.: "In Vitro Self-Renewal Division of Hematopoietic Stem Cells."J Exp Med. Vol.192. 1281-1288 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hideo Ema and Hiromitsu Nakauchi: "Expanshion of hematopoietic stem cells in the developing liver of a mouse embryo."Blood. Vol.95. 2284-2288 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiki Y et al.: "Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments."Exp Hematol. Vol.28. 792-801 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakauchi H et al.: "Cell Therapy"Springer-Verlag Tokyo. 240 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] I.Aposolou,et al.: "Murine natural killer cells contribute to the granulomatous reaction caused by mycobacterial cell walls."Proc Natl Acad Sci USA. 96. 5141-5146 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken-ichi Matsuda,et al.: "A Novel Stromal Cell-Dependent B Lymphoid Stem-Like Cell Line That Induces Immunoglobulin Gene Rearrangement."J.Biochem.. 125. 602-612 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomoyuki Yamaguchi,et al.: "Human Immunodeficiency Virus Type 1 Vpr Modifies Cell Proliferation via Multiple Pathways."Microbiol.Immunol.. 43. 437-447 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hideyuki Murata,et al.: "Microchimerism in Japanese women patients with systemic sclerosis."The Lancet.. 354. 220 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] DONG Ku Kim*,YUTAKA FUJIKI*,et al.: "Comparison of Hematopoietic Activities of Human Bone Marrow and Umbilical Code Blood CD34 Positive and Negative Cells."STEM CELLS. 17. 286-294 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazuo Shibuya,et al.: "Physical and Functional Association of LFA-1 with DNAM-1 Adhesion Molecule."Immunity. 11. 615-623 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiromitsu Nakauchi.: "The Hematopoietic Stem Cell.edited by Shirkis,Orlic and Kantz."Academic Press. 14 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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