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The severe combined immunodeficient-human peripheral blood stem cell
(SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated
hematopoiesis
SR Goan, I Fichtner, U Just, L Karawajew, W Schultze, KP Krause, S von Harsdorf, C von Schilling and F Herrmann
Department of Medical Oncology and Applied Molecular Biology, University
Clinics Rudolf Virchow, Robert-Rossle Cancer Center, Free University of
Berlin, Germany.
Mononuclear cells (MNCs) containing peripheral blood stem cells (PBSCs)
were obtained from solid-tumor patients undergoing mobilizing chemotherapy
followed by granulocyte colony-stimulating factor for PBSC
transplantation-supported dose-intensified anticancer chemotherapy and were
transplanted into unconditioned "nonleaky" young severe combined
immunodeficient mice. Multilineage engraftment was shown by flow cytometry
and immunocytochemistry using monoclonal antibodies to various human cell
surface antigens as well as identification of human immunoglobulin in
murine sera. Within a dose range of MNCs suitable for transplantation (10
to 36 x 10(6) cells/graft) the number of CD34+ cells injected (optimal at
> 0.7 x 10(6)/graft) determined the yield of human cells produced in
recipient animals. Engraftment of hu PBSC preparations resulted in
prolonged generation of physiologic levels of human cytokines including
interleukin-3 (IL-3), IL-6, and granulocyte- macrophage colony-stimulating
factor, which were detectable in the murine blood over a period of at least
4 months. In vivo survival of immature human progenitor cells was preserved
even 9 months after transplantation. Because human IL-3 is known to
stimulate early hematopoiesis, a rat fibroblast cell line was stably
transfected with a retroviral vector carrying the human IL-3 gene and
cotransplanted subcutaneously as additional source of growth factor.
Cotransplants of this cell line producing sustained in vivo levels of
circulating human IL-3 for at least 12 weeks significantly accelerated the
process of engraftment of huPBSC and spurred the spread of mature human
cells to the murine spleen, liver, thymus, and peripheral blood.
Cotransplants of allogeneic human bone marrow stromal cells derived from
long-term cultures resulted in a comparable--though less prominent--support
of engraftment.
Volume 86,
Issue 1,
pp. 89-100,
07/01/1995
Copyright © 1995 by The American Society of Hematology
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