title: 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.
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/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.
authors.affiliation: Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06509, USA.
authors.forename: Christin M
authors.initials: CM
authors.lastname: Lepus
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gibson
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
authors.forename: Ivana
authors.initials: I
authors.lastname: Kawikova
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
authors.forename: Jaber
authors.initials: J
authors.lastname: Hossain
authors.forename: Vitaly
authors.initials: V
authors.lastname: Ablamunits
authors.forename: Nancy
authors.initials: N
authors.lastname: Kirkiles-Smith
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Bothwell
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Harding
mesh_terms: D000818:Animals; D005312:Fetal Blood / Q000276:immunology*; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007136:Immunoglobulins / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D008099:Liver / Q000196:embryology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D011829:Radiation Dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014916:Whole-Body Irradiation
chemical_list: D007136:Immunoglobulins; D016179:Granulocyte Colony-Stimulating Factor; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin