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

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.