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Effective expansion of engrafted human hematopoietic stem cells in bone marrow of mice expressing human Jagged-1

Authors
  • Negishi, Naoko
  • Suzuki, Daisuke
  • Ito, Ryoji
  • Irie, Naoko
  • Matsuo, Koichi
  • Yahata, Takashi
  • Nagano, Kenichi
  • Aoki, Kazuhiro
  • Ohya, Keiichi
  • Hozumi, Katsuto
  • Ando, Kiyoshi
  • Tamaoki, Norikazu
  • Ito, Mamoru
  • Habu, Sonoko1, 2, 1, 3, 4, 5, 6, 7, 8, 9, 10, 3, 11, 12, 13, 14
  • 1 Department of Immunology
  • 2 Juntendo University School of Medicine
  • 3 Tokai University School of Medicine
  • 4 Department of Animal Biology
  • 5 University of Pennsylvania School of Veterinary Medicine
  • 6 Central Institute for Experimental Animals
  • 7 Laboratory of Cell and Tissue Biology
  • 8 Keio University School of Medicine
  • 9 Division of Hematopoiesis
  • 10 Research Center for Regenerative Medicine and Department of Hematology
  • 11 Section of Pharmacology
  • 12 Department of Bio-Matrix
  • 13 Tokyo Medical and, Dental University
  • 14 1-5-45 Yushima
Type
Published Article
Journal
Experimental Hematology
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Feb 03, 2014
Identifiers
DOI: 10.1016/j.exphem.2014.02.001
Source
Elsevier
Keywords
License
Unknown

Abstract

The human immune system can be reconstituted in experimental animals by transplanting human hematopoietic stem cells (hHSCs) into immunodeficient mice. To generate such humanized mice, further improvements are required, particularly to ensure that transplanted hHSCs are maintained in mice and proliferate long enough to follow prolonged immune responses to chronic diseases or monitor therapeutic effects. To prepare the relatively human bone marrow environment in mice, we generated non-obese diabetic/severe combined immunodeficiency/IL-2 receptor gamma chain null (NOG) mice expressing human Jagged1 (hJ1) in an osteoblast-specific manner (hJ1-NOG mice) to examine whether Notch signaling induced by hJ1 mediates hHSC proliferation and/or maintenance in mice. The established hJ1-NOG mice possess relatively larger bone marrow (BM) space and thinner cortical bone compared to non-transgenic littermates but the number of c-kit+ Sca-1+ lineage- (KSL) cells was not significantly different between hJ1-NOG and non-transgenic littermates. In the transplantation experiments of CD34+ cells obtained from human cord blood, CD34+CD38- cells (hHSCs) were more increased in hJ1-NOG recipient mice than in non-transgenic littermates in mouse BM environment. In contrast, the transplanted mouse KSL cells did not show significant increase in the same hJ1-NOG mice. These results suggest that hJ1-NOG mice could contribute to the growth of transplanted human CD34+ cells in a human specific manner and be useful to study the in vivo behavior and/or development of human stem cells including cancer stem cells and immune cells.

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