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.
Namikawa
R
R
SyStemix, Inc., Palo Alto, California 94303.
Weilbaecher
K N
KN
Kaneshima
H
H
Yee
E J
EJ
McCune
J M
JM
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