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The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis

Item Type:Article
Title:The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis
Creators Name:Goan, S.R. and Fichtner, I. and Just, U. and Karawajew, L. and Schultze, W. and Krause, K.P. and von Harsdorf, S. and von Schilling, C. and Herrmann, F.
Abstract: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.
Keywords:Antibody Formation, Antineoplastic Combined Chemotherapy Protocols, Bleomycin, Bone Marrow Transplantation, Breast Neoplasms, Cell Line, Chimera, Cisplatin, Cyclophosphamide, Epirubicin, Etoposide, Fibroblasts, Fluorouracil, Graft Survival, Granulocyte Colony-Stimulating Factor, Hematopoietic Cell Growth Factors, Hematopoietic Stem Cell Transplantation, Ifosfamide, Interleukin-3, Lymphoid Tissue, Ovarian Neoplasms, Severe Combined Immunodeficiency, Testicular Neoplasms, Heterologous Transplantation, Animals, Mice
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:86
Number:1
Page Range:89-100
Date:1 July 1995
Official Publication:http://bloodjournal.hematologylibrary.org/cgi/content/abstract/86/1/89
PubMed:View item in PubMed

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