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

Christin M. Lepus, Thomas F. Gibson, Scott A. Gerber, Ivana Kawikova, Marian Szczepanik, Jaber Hossain, Vitaly Ablamunits, Nancy Kirkiles-Smith, Kevan C. Herold, Ruben O. Donis, Alfred L. Bothwell, Jordan S. Pober, Martha J. Harding

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

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/γc-/-, Balb/c-Rag1-/-γc-/-, and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/γc-/- and Balb/c-Rag1-/-γc-/- harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/γc-/- mice harbored higher levels of human T cells. NOD-scid/γc-/- 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/γc-/- mice that is well suited for future studies toward the development of a fully competent humanized mouse model.

Original languageEnglish (US)
Pages (from-to)790-802
Number of pages13
JournalHuman Immunology
Volume70
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • Delayed-type hypersensitivity
  • Hematopoietic stem cell
  • Human immune system development
  • Isotype switching
  • Mouse model

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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