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2001 Fiscal Year Final Research Report Summary

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
Keywordsin utero transplantation / in utero gene therapy / hematopoietic stem cells / crab-eatingmonkey / retroviralvector / microchimerism
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.

  • Research Products

    (27 results)

All Other

All Publications (27 results)

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

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  • [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)

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

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  • [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)

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  • [Publications] Hiromitsu Nakauchi, et al.: "Quantitative assessment of the stem cell self-renewal capacity"Ann N Y Acad Sci. 938巻. 18-25 (2001)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [Publications] Sudo K, Ema H, Morita Y, Nakauchi H: "Aoe-associated characteristics of murine hematopoietic stem cells"J Exp Med. 192. 1273-80 (2000)

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  • [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)

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  • [Publications] Hideo Ema, Hiromitsu Nakauchi: "Expanshion of hematopoietic stem cells in the developing liver of a mouse embryo"Blood. 95. 2284-8 (2000)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [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)

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  • [Publications] Hideyuki Murata, Hiromitsu Nakauchi, Takayuki Sumida: "Microchimerism in Japanease women patients with systemic sclerosis"The Lancet. 354. 220 (1999)

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  • [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)

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Published: 2003-09-17  

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