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Biology of Human Hematopoietic Stem Cell Xenotransplantation in Mice

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Abstract

Xenotransplantation of human hematopoietic stem cells into immunodeficient mice is essential to create humanized mice with human hematopoietic and lymphoid cells. The failure of hematopoietic stem cell transplantation across species can be caused not only by immune rejection but also by the unfavorable hematopoietic microenvironment in a xenogeneic recipient. The use of currently available immunodeficient mice can prevent xenograft rejection by T, B, and natural killer cells; however, antibody-independent innate immune responses remain a significant hurdle for making humanized mice with all lineages of human blood cells. The species specificity of cytokines and adhesion molecules essential to hematopoiesis clearly presents obstacles to the engraftment and differentiation of human hematopoietic stem cells in mice. In this chapter, we discuss the biology of human hematopoietic stem cell xenotransplantation in immunodeficient mice and possible mechanisms causing poor reconstitution of human red blood cells and platelets.

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Abbreviations

HSC:

Hematopoietic stem cell

HHLS:

Human hematopoietic and lymphoid systems

SCID:

Severe combined immune deficiency

Prkdc:

DNA-dependent protein kinase, catalytic subunit

RAG:

Recombination activating gene

SIRPα:

Signaling regulatory protein alpha

EPO:

Erythropoietin

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

M-CSF:

Macrophage colony stimulating

NOD:

Nonobese diabetic

NSG:

NOD/SCID IL2 receptor gamma chain knockout

TCD:

T cell-depleted

RBCs:

Red blood cells

TPO:

Thrombopoietin

WBCs:

White blood cells

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Acknowledgments

The work from the authors’ laboratories discussed in this chapter was supported by grants from the National Institutes of Health (NIH) (R01 AI064569, and P01AI045897), Chinese Ministry of Science and Technology (2015CB964400), Chinese Ministry of Education (IRT1133),NSFC (81273334 and 81200397).

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Authors and Affiliations

  1. First Hospital of Jilin University, Changchun, China

    Zheng Hu & Yong-Guang Yang MD

  2. Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons, New York, NY, USA

    Yong-Guang Yang MD

Authors
  1. Zheng Hu
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Corresponding author

Correspondence to Yong-Guang Yang MD .

Editor information

Editors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Larisa Y. Poluektova

  2. Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    J. Victor Garcia

  3. Research Center for AIDS Laboratory of Viral Pathogenesis, Kyoto University Institute for Virus Research, Sakyo-ku, Japan

    Yoshio Koyanagi

  4. Division of Hematology, University Hospital Zürich, Zürich, Switzerland

    Markus G. Manz

  5. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    Andrew M. Tager

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Hu, Z., Yang, YG. (2014). Biology of Human Hematopoietic Stem Cell Xenotransplantation in Mice. In: Poluektova, L., Garcia, J., Koyanagi, Y., Manz, M., Tager, A. (eds) Humanized Mice for HIV Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1655-9_5

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