title: Retention and multilineage expression of human hematopoietic stem cells in human-sheep chimeras.
abstract: We have taken advantage of the permissive environment of the early gestational age fetus to engraft human hematopoietic stem cells (HSC) into preimmune fetal lambs. The resulting chimeras exhibit long-term multilineage engraftment of human cells in the bone marrow (BM) and peripheral blood (PB). Long-term multilineage reconstitution of second generation recipients by human cells isolated from chimeric sheep BM indicates that the engraftment in this model involved long-term repopulating human HSC. The model appears to be sensitive enough to detect relatively small numbers of transplanted HSC from pre- and postnatal human sources. Finally, transplantation of mature T lymphocyte-containing cells from a variety of sources results in lethal graft-versus-host disease (GVHD), analogous to clinical BM transplantation, suggesting that, at least in some respects, the model is biologically relevant. The human-sheep model is promising and may have important advantages over murine models for the in vivo study of normal and abnormal hematopoiesis and as a potential assay system for human HSC.
authors.affiliation: Department of Medicine, Department of Veterans Affairs Medical Center, Medicine, Reno, NV 89520, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Zanjani
authors.forename: G
authors.initials: G
authors.lastname: Almeida-Porada
authors.forename: A W
authors.initials: AW
authors.lastname: Flake
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002678:Chimera; D003114:Colony-Forming Units Assay; D016332:Fetal Tissue Transplantation; D005333:Fetus; D018380:Hematopoietic Stem Cell Transplantation; D008099:Liver / Q000196:embryology; D012756:Sheep; D014183:Transplantation, Heterologous
chemical_list: D015703:Antigens, CD; D015415:Biomarkers