Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/gammac-/-, Balb/c-Rag1-/-gammac-/-, and C.B-17-scid/bg immunodeficient mice

Hum Immunol. 2009 Oct;70(10):790-802. doi: 10.1016/j.humimm.2009.06.005. Epub 2009 Jun 12.


Immunodeficient mice bearing components of a human immune system present a novel approach for studying human immune responses. We investigated the number, phenotype, developmental kinetics, and function of developing human immune cells following transfer of CD34(+) hematopoietic stem cell (HSC) preparations originating from second trimester human fetal liver (HFL), umbilical cord blood (UCB), or granulocyte colony-stimulating factor-mobilized adult blood (G-CSF-AB) delivered via intrahepatic injection into sublethally irradiated neonatal NOD-scid/gammac(-/-), Balb/c-Rag1(-/-)gammac(-/-), and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/gammac(-/-) and Balb/c-Rag1(-/-)gammac(-/-) harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/gammac(-/-) mice harbored higher levels of human T cells. NOD-scid/gammac(-/-) mice engrafted with HFL CD34(+) HSC demonstrated human immunological competence evidenced by white pulp expansion and increases in total human immunoglobulin following immunization with T-dependent antigens and delayed-type hypersensitivity-infiltrating leukocytes in response to antigenic challenge. In conclusion, we describe an encouraging base system for studying human hematopoietic lineage development and function utilizing human HFL or UCB HSC-engrafted NOD-scid/gammac(-/-) mice that is well suited for future studies toward the development of a fully competent humanized mouse model.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fetal Blood / immunology*
  • Granulocyte Colony-Stimulating Factor / immunology
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / immunology*
  • Hematopoietic Stem Cells / metabolism
  • Hemocyanins / immunology
  • Humans
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / pathology
  • Immunoglobulins / blood
  • Influenza A Virus, H5N1 Subtype / immunology
  • Liver / embryology
  • Liver / immunology*
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Radiation Dosage
  • Spleen / cytology
  • Spleen / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Whole-Body Irradiation


  • Immunoglobulins
  • Granulocyte Colony-Stimulating Factor
  • Hemocyanins
  • keyhole-limpet hemocyanin