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

2.50
Hdl Handle:
http://hdl.handle.net/10541/97488
Title:
The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis.
Authors:
Goan, S R; Fichtner, Iduna; Just, Ursula; Karawajew, L; Schultze, W; Krause, K P; Von Harsdorf, S; Von Schilling, C; 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.
Affiliation:
Department of Medical Oncology and Applied Molecular Biology, University Clinics Rudolf Virchow, Robert-Rössle Cancer Center, Free University of Berlin, Germany.
Citation:
The severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis. 1995, 86 (1):89-100 Blood
Journal:
Blood
Issue Date:
1-Jul-1995
URI:
http://hdl.handle.net/10541/97488
PubMed ID:
7540891
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorGoan, S Ren
dc.contributor.authorFichtner, Idunaen
dc.contributor.authorJust, Ursulaen
dc.contributor.authorKarawajew, Len
dc.contributor.authorSchultze, Wen
dc.contributor.authorKrause, K Pen
dc.contributor.authorVon Harsdorf, Sen
dc.contributor.authorVon Schilling, Cen
dc.contributor.authorHerrmann, Fen
dc.date.accessioned2010-04-27T14:33:52Z-
dc.date.available2010-04-27T14:33:52Z-
dc.date.issued1995-07-01-
dc.identifier.citationThe severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis. 1995, 86 (1):89-100 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid7540891-
dc.identifier.urihttp://hdl.handle.net/10541/97488-
dc.description.abstractMononuclear 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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectHaematopoiesisen
dc.subjectHaematopoietic Cell Growth Factorsen
dc.subjectHaematopoietic Stem Cell Transplantationen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectOvarian Canceren
dc.subjectTesticular Canceren
dc.subject.meshAdult-
dc.subject.meshAnimals-
dc.subject.meshAntibody Formation-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshBleomycin-
dc.subject.meshBone Marrow Transplantation-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCell Line-
dc.subject.meshChimera-
dc.subject.meshCisplatin-
dc.subject.meshCyclophosphamide-
dc.subject.meshEpirubicin-
dc.subject.meshEtoposide-
dc.subject.meshFemale-
dc.subject.meshFibroblasts-
dc.subject.meshFluorouracil-
dc.subject.meshGraft Survival-
dc.subject.meshGranulocyte Colony-Stimulating Factor-
dc.subject.meshHematopoiesis-
dc.subject.meshHematopoietic Cell Growth Factors-
dc.subject.meshHematopoietic Stem Cell Transplantation-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshIfosfamide-
dc.subject.meshInterleukin-3-
dc.subject.meshLymphoid Tissue-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, SCID-
dc.subject.meshMiddle Aged-
dc.subject.meshOvarian Neoplasms-
dc.subject.meshRats-
dc.subject.meshSevere Combined Immunodeficiency-
dc.subject.meshTesticular Neoplasms-
dc.subject.meshTransplantation, Heterologous-
dc.titleThe severe combined immunodeficient-human peripheral blood stem cell (SCID-huPBSC) mouse: a xenotransplant model for huPBSC-initiated hematopoiesis.en
dc.typeArticleen
dc.contributor.departmentDepartment of Medical Oncology and Applied Molecular Biology, University Clinics Rudolf Virchow, Robert-Rössle Cancer Center, Free University of Berlin, Germany.en
dc.identifier.journalBlooden

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