SEARCH:   Advanced

Blood, 1 September 2005, Vol. 106, No. 5, pp. 1565-1573. Prepublished online as a Blood First Edition Paper on May 26, 2005; DOI 10.1182/blood-2005-02-0516. This Article Full Text (PDF) Supplemental Table All Versions of this Article: 2005-02-0516v1 106/5/1565    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ishikawa, F. Articles by Harada, M. Search for Related Content PubMed PubMed Citation Articles by Ishikawa, F. Articles by Harada, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2005 Accepted April 7, 2005 Development of functional human blood and immune systems in NOD/SCID/IL2 receptor chainnull mice Fumihiko Ishikawa, Masaki Yasukawa, Bonnie Lyons, Shuro Yoshida, Toshihiro Miyamoto, Goichi Yoshimoto, Takeshi Watanabe, Koichi Akashi*, Leonard D Shultz, and Mine Harada Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan First Department of Internal Medicine, Ehime University School of Medicine, Shigenobu, Japan The Jackson Laboratory, Bar Harbor, ME, USA Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan RIKEN for Allergy and Immunology, Yokohama, Japan Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan; Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA * Corresponding author; email: koichi_akashi{at}dfci.harvard.edu. Here we report that a new NOD/SCID mouse line harboring a complete null mutation of the common cytokine receptor chain (NOD/SCID/IL2rnull) efficiently supports development of functional human hemato-lymphopoiesis. Purified human hCD34+ or hCD34+hCD38- cord blood (CB) cells were transplanted into NOD/SCID/IL2rnull newborns via a facial vein. In all recipients injected with 105 hCD34+ or 2x104 hCD34+hCD38- CB cells, human hematopoietic cells were reconstituted at ~70% of chimerisms. A high percentage of the human hematopoietic cell chimerism persisted for > 24 weeks after transplantation, and hCD34+ bone marrow grafts of primary recipients could reconstitute hematopoiesis in secondary NOD/SCID/IL2rnull recipients, suggesting that this system can support self-renewal of human hematopoietic stem cells. hCD34+hCD38- CB cells differentiated into mature blood cells, including myelomonocytes, dendritic cells, erythrocytes, platelets, and lymphocytes. Differentiation into each lineage occurred via developmental intermediates such as common lymphoid progenitors and common myeloid progenitors, recapitulating the steady-state human hematopoiesis. B cells underwent normal class switching, and produced antigen-specific immunoglobulins. T cells displayed the HLA-dependent cytotoxic function. Furthermore, human IgA-secreting B cells were found in the intestinal mucosa, suggesting reconstitution of human mucosal immunity. Thus, the NOD/SCID/IL2rnull newborn system might be an important experimental model to study human hemato-lymphoid system. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Hattori, K. Ide, H. Nakata, H. Harada, S. Suzu, N. Ashida, S. Kohgo, H. Hayakawa, H. Mitsuya, and S. Okada Potent Activity of a Nucleoside Reverse Transcriptase Inhibitor, 4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine, against Human Immunodeficiency Virus Type 1 Infection in a Model Using Human Peripheral Blood Mononuclear Cell-Transplanted NOD/SCID Janus Kinase 3 Knockout Mice Antimicrob. Agents Chemother., September 1, 2009; 53(9): 3887 - 3893. [Abstract] [Full Text] [PDF] J. Mota and R. Rico-Hesse Humanized Mice Show Clinical Signs of Dengue Fever according to Infecting Virus Genotype J. Virol., September 1, 2009; 83(17): 8638 - 8645. [Abstract] [Full Text] [PDF] J. Unsinger, J. S. McDonough, L. D. Shultz, T. A. Ferguson, and R. S. Hotchkiss Sepsis-induced human lymphocyte apoptosis and cytokine production in "humanized" mice J. Leukoc. Biol., August 1, 2009; 86(2): 219 - 227. [Abstract] [Full Text] [PDF] D. M. Brainard, E. Seung, N. Frahm, A. Cariappa, C. C. Bailey, W. K. Hart, H.-S. Shin, S. F. Brooks, H. L. Knight, Q. Eichbaum, et al. Induction of Robust Cellular and Humoral Virus-Specific Adaptive Immune Responses in Human Immunodeficiency Virus-Infected Humanized BLT Mice J. Virol., July 15, 2009; 83(14): 7305 - 7321. [Abstract] [Full Text] [PDF] Y. Watanabe, T. Takahashi, A. Okajima, M. Shiokawa, N. Ishii, I. Katano, R. Ito, M. Ito, M. Minegishi, N. Minegishi, et al. The analysis of the functions of human B and T cells in humanized NOD/shi-scid/{gamma}cnull (NOG) mice (hu-HSC NOG mice) Int. Immunol., July 1, 2009; 21(7): 843 - 858. [Abstract] [Full Text] [PDF] T. Strowig, C. Gurer, A. Ploss, Y.-F. Liu, F. Arrey, J. Sashihara, G. Koo, C. M. Rice, J. W. Young, A. Chadburn, et al. Priming of protective T cell responses against virus-induced tumors in mice with human immune system components J. Exp. Med., June 8, 2009; 206(6): 1423 - 1434. [Abstract] [Full Text] [PDF] M. Kai, T. Hagiwara, C. Emuta, Y. Chisaka, K. Tsuruhata, C. Endo, Y. Inagaki, H. Miyazaki, and S. Kataoka In vivo efficacy of anti-MPL agonist antibody in promoting primary human hematopoietic cells Blood, March 5, 2009; 113(10): 2213 - 2216. [Abstract] [Full Text] [PDF] J. E. Dick Stem cell concepts renew cancer research Blood, December 15, 2008; 112(13): 4793 - 4807. [Abstract] [Full Text] [PDF] S. T. Chou, J. B. Opalinska, Y. Yao, M. A. Fernandes, A. Kalota, J. S. J. Brooks, J. K. Choi, A. M. Gewirtz, G.-a. Danet-Desnoyers, R. L. Nemiroff, et al. Trisomy 21 enhances human fetal erythro-megakaryocytic development Blood, December 1, 2008; 112(12): 4503 - 4506. [Abstract] [Full Text] [PDF] W. Nogami, H. Yoshida, K. Koizumi, H. Yamada, K. Abe, A. Arimura, N. Yamane, K. Takahashi, A. Yamane, A. Oda, et al. The effect of a novel, small non-peptidyl molecule butyzamide on human thrombopoietin receptor and megakaryopoiesis Haematologica, October 1, 2008; 93(10): 1495 - 1504. [Abstract] [Full Text] [PDF] C. Gurer, T. Strowig, F. Brilot, M. Pack, C. Trumpfheller, F. Arrey, C. G. Park, R. M. Steinman, and C. Munz Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses Blood, August 15, 2008; 112(4): 1231 - 1239. [Abstract] [Full Text] [PDF] L. J. Giassi, T. Pearson, L. D. Shultz, J. Laning, K. Biber, M. Kraus, B. A. Woda, M. R. Schmidt, R. T. Woodland, A. A. Rossini, et al. Expanded CD34+ Human Umbilical Cord Blood Cells Generate Multiple Lymphohematopoietic Lineages in NOD-scid IL2r{gamma}null Mice Experimental Biology and Medicine, August 1, 2008; 233(8): 997 - 1012. [Abstract] [Full Text] [PDF] D. Nguyen and T. Xu The expanding role of mouse genetics for understanding human biology and disease Dis. Model. Mech., July 1, 2008; 1(1): 56 - 66. [Abstract] [Full Text] [PDF] Y. Kikushige, G. Yoshimoto, T. Miyamoto, T. Iino, Y. Mori, H. Iwasaki, H. Niiro, K. Takenaka, K. Nagafuji, M. Harada, et al. Human Flt3 Is Expressed at the Hematopoietic Stem Cell and the Granulocyte/Macrophage Progenitor Stages to Maintain Cell Survival J. Immunol., June 1, 2008; 180(11): 7358 - 7367. [Abstract] [Full Text] [PDF] M. R. Simpson-Abelson, G. F. Sonnenberg, H. Takita, S. J. Yokota, T. F. Conway Jr., R. J. Kelleher Jr., L. D. Shultz, M. Barcos, and R. B. Bankert Long-Term Engraftment and Expansion of Tumor-Derived Memory T Cells Following the Implantation of Non-Disrupted Pieces of Human Lung Tumor into NOD-scid IL2R{gamma}null Mice J. Immunol., May 15, 2008; 180(10): 7009 - 7018. [Abstract] [Full Text] [PDF] N. Tonomura, K. Habiro, A. Shimizu, M. Sykes, and Y.-G. Yang Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model Blood, April 15, 2008; 111(8): 4293 - 4296. [Abstract] [Full Text] [PDF] H. H. Wandall, K. M. Hoffmeister, A. L. Sorensen, V. Rumjantseva, H. Clausen, J. H. Hartwig, and S. J. Slichter Galactosylation does not prevent the rapid clearance of long-term, 4{degrees}C-stored platelets Blood, March 15, 2008; 111(6): 3249 - 3256. [Abstract] [Full Text] [PDF] F. Ishikawa, H. Niiro, T. Iino, S. Yoshida, N. Saito, S. Onohara, T. Miyamoto, H. Minagawa, S.-i. Fujii, L. D. Shultz, et al. The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways Blood, November 15, 2007; 110(10): 3591 - 3660. [Abstract] [Full Text] [PDF] A.-L. Sellier-Leclerc, A. Duval, S. Riveron, M.-A. Macher, G. Deschenes, C. Loirat, M.-C. Verpont, M. Peuchmaur, P. Ronco, R. C. Monteiro, et al. A Humanized Mouse Model of Idiopathic Nephrotic Syndrome Suggests a Pathogenic Role for Immature Cells J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2732 - 2739. [Abstract] [Full Text] [PDF] S. Malarkannan, J. Regunathan, H. Chu, S. Kutlesa, Y. Chen, H. Zeng, R. Wen, and D. Wang Bcl10 Plays a Divergent Role in NK Cell-Mediated Cytotoxicity and Cytokine Generation J. Immunol., September 15, 2007; 179(6): 3752 - 3762. [Abstract] [Full Text] [PDF] D. S. An, B. Poon, R. H. T. Fang, K. Weijer, B. Blom, H. Spits, I. S. Y. Chen, and C. H. Uittenbogaart Use of a Novel Chimeric Mouse Model with a Functionally Active Human Immune System To Study Human Immunodeficiency Virus Type 1 Infection Clin. Vaccine Immunol., April 1, 2007; 14(4): 391 - 396. [Abstract] [Full Text] [PDF] L. Zhang, G. I. Kovalev, and L. Su HIV-1 infection and pathogenesis in a novel humanized mouse model Blood, April 1, 2007; 109(7): 2978 - 2981. [Abstract] [Full Text] [PDF] S. Gorantla, H. Sneller, L. Walters, J. G. Sharp, S. J. Pirruccello, J. T. West, C. Wood, S. Dewhurst, H. E. Gendelman, and L. Poluektova Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2-/-{gamma}c-/- Mice J. Virol., March 15, 2007; 81(6): 2700 - 2712. [Abstract] [Full Text] [PDF] S. Baenziger, R. Tussiwand, E. Schlaepfer, L. Mazzucchelli, M. Heikenwalder, M. O. Kurrer, S. Behnke, J. Frey, A. Oxenius, H. Joller, et al. Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-{gamma}c-/- mice PNAS, October 24, 2006; 103(43): 15951 - 15956. [Abstract] [Full Text] [PDF] F. Ishikawa, H. Shimazu, L. D. Shultz, M. Fukata, R. Nakamura, B. Lyons, K. Shimoda, S. Shimoda, T. Kanemaru, K.-i. Nakamura, et al. Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion FASEB J, May 1, 2006; 20(7): 950 - 952. [Abstract] [Full Text] [PDF] N. Legrand, K. Weijer, and H. Spits Experimental Models to Study Development and Function of the Human Immune System In Vivo J. Immunol., February 15, 2006; 176(4): 2053 - 2058. [Abstract] [Full Text] [PDF] F. Macchiarini, M. G. Manz, A. K. Palucka, and L. D. Shultz Humanized mice: are we there yet? J. Exp. Med., November 21, 2005; 202(10): 1307 - 1311. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020