Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Immune-deficient mice as models for human hematopoietic disease.
Mol Genet Med; 1:77-115 1991. Unique Identifier : AIDSLINE ICDB/93690248 Dick JE; Dept. of Genetics, Res. Inst., Hosp. for Sick Children, Toronto,; Ontario, Canada
Abstract:
Knowledge of the hematopoietic cell system has been derived primarily from studies of the mouse. In vivo assays for the various cells within the stem cell hierarchy have played an important role in these advances. In contrast, understanding of the biology of the human hematopoietic system has suffered because of the lack of in vivo assays for pluripotent stem cells. The recently described systems of transplanting human hematopoietic cells into immune-deficient mice may overcome this limitation and lay the foundation for manipulating human hematopoietic cells in ways previously only feasible in mice. Equally important will be the establishment of animal models of many human diseases that affect the hematopoietic system. The development of these animal models is reviewed, and an overview is provided of the basic concepts of mouse and human hematopoiesis that governed development of the models. Topics include hematopoiesis (murine stem cells, murine progenitor cells, human hematopoiesis, leukemic transformation, and growth factors); genetic manipulation of hematopoietic stem cells (characterization of retrovirus-infected hematopoietic stem cells and retrovirus gene transfer into human hematopoietic cells); engraftment of human hematopoietic cells in immune-deficient mice (recipient mice, engraftment of human bone marrow, engraftment of mature peripheral blood lymphocytes, and engraftment of human fetal organs); and applications (models of human leukemia, Epstein-Barr virus transformation in vivo, solid tumors, HIV infection, and autoimmune diseases). The growth of human hematopoietic cells in immune-deficient mice promises to revolutionize the study of normal developmental programs of human hematopoiesis and the biological consequences of aberrant proliferation and differentiation. The engraftment of hematopoietic cells directly from patients with disease ultimately should lead to animal models for many human hemopathies and leukemias. Already, important preliminary experiments have established the feasibility of such models for leukemia, cancer, infectious diseases, and autoimmunity. The production of human antibodies directed against toxic agents for which humans cannot be immunized could provide the basis for improved pharmaceuticals. (107 Refs)
Keywords: Animal Bone Marrow Diseases/GENETICS/*PATHOLOGY Cell Transformation, Neoplastic Disease Models, Animal Feasibility Studies *Hematopoiesis Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells/TRANSPLANTATION Mice Mice, SCID MONOGRAPH 930430
M9340832
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
