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

• Published in: Human immunology 2009-10, Vol.70 (10), p.790-802
• Main Authors: Lepus, C M, Gibson, T F, Gerber, SA, Kawikova, I, Szczepanik, M, Hossain, J, Ablamunits, V, Kirkiles-Smith, N, Herold, K C, Donis, RO, Bothwell, AL, Pober, J S, Harding, MJ
• Format: Article
• Language: English
• ISSN: 0198-8859
• DOI: 10.1016/j.humimm.2009.06.005

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 super(+) 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/ gamma c super(-) super(/) super(-), Balb /c-Rag1 super(-) super(/) super(-) gamma c super(-) super(/) super(-), and C.B-17-scid/bg mice. HFL and UCB HSC provided the greatest number and breadth of developing cells. NOD-scid/ gamma c super(-) super(/) super(-) and Balb/c-Rag1 super(-) super(/) super(-) gamma c super(-) super(/) super(-) harbored human B and dendritic cells as well as human platelets in peripheral blood, whereas NOD-scid/ gamma c super(-) super(/) super(-) mice harbored higher levels of human T cells. NOD-scid/ gamma c super(-) super(/) super(-) mice engrafted with HFL CD34 super(+) 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/ gamma c super(-) super(/) super(-) mice that is well suited for future studies toward the development of a fully competent humanized mouse model.