Long-term human hematopoiesis in the SCID-hu mouse.
Coimplantation of small fragments of human fetal thymus and fetal liver into immunodeficient SCID mice resulted in the formation of a unique structure (Thy/Liv). Thereafter, the SCID-hu mice showed reproducible and long-term reconstitution of human hematopoietic activity. For periods lasting 5-11 mo after transplantation, active T lymphopoiesis was observed inside the grafts and cells that were negative for T cell markers were found to have colony-forming units for granulocyte/macrophage (CFU-GM) and erythroid burst-forming unit (BFU-E) activity in the methylcellulose colony assay. In addition, structures similar to normal human bone marrow were observed inside the Thy/Liv grafts, consisting of blast cells, mature and immature forms of myelomonocytic cells, and megakaryocytes. These data indicate long-term maintenance, in vivo, of human progenitor cells for the T lymphoid, myelomonocytic, erythroid, and megakaryocytic lineages. The role of the implanted fetal liver fragments was analyzed using HLA-mismatched Thy/Liv implants. The HLA type of the liver donor was found on T cells and macrophages in the graft. In addition, cells grown in the methylcellulose colony assay and cells in a bone marrow-like structure, the "thymic isle," expressed the HLA type of the liver donor. Thus, the Thy/Liv implants provided a microenvironment in which to follow human hematopoietic progenitor cells for multiple lineages. The formation of the Thy/Liv structures also results in a continuous source of human T cells in the peripheral circulation of the SCID-hu mouse. Though present for 5-11 mo, these cells did not engage in a xenograft (graft-versus-host) reaction. This animal model, the first in which multilineage human hematopoietic activity is maintained for long periods of time, should be useful for the analysis of human hematopoiesis in vivo.
SyStemix, Inc., Palo Alto, California 94303.
R
R
Namikawa
K N
KN
Weilbaecher
H
H
Kaneshima
E J
EJ
Yee
J M
JM
McCune
D000818:Animals; D016332:Fetal Tissue Transplantation; D006086:Graft vs Host Disease; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000503:physiopathology; D016031:Liver Transplantation; D051379:Mice; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000502:physiology; D013950:Thymus Gland / Q000637:transplantation