Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T et al. Cytokine treatment of accessory cells are required to initiate engraftment of purified primitive human hematopoietic cells transplanted at limiting doses into NOD/SCID mice. Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse as a model system to study the engraftment and mobilization of human peripheral blood stem cells. Van der Loo JCM, Hanenberg H, Cooper RJ, Luo F-Y, Lazaridis EN, Williams DA. Human growth factor-enhanced regeneration of transplantable human hematopoietic stem cells in nonobese diabetic/severe combined immunodeficient mice. Kinetic evidence of the regeneration of multilineage hematopoiesis from primitive cells in normal human bone marrow transplanted into immunodeficient mice. J Immunol 1995 154: 180–191.Ĭashman JD, Lapidot T, Wang JCY, Doedens M, Shultz LD, Lansdorp P et al. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. Shultz LD, Schweitzer PA, Christianson SW, Gott B, Schweitzer IB, Tennent B et al. New York: Oxford University Press, 2001, pp 99–118. In: Zon LI (ed) Hematopoiesis A Developmental Approach. Normal and leukemic human stem cells assayed in immune-deficient mice. Wang JCY, Dorrell C, Ito CY, Inamitsu T, Guenechea G, Gan OI et al. Our findings suggest that long-term exposure of primitive human hematopoietic cells to elevated levels of human IL-3, GM-CSF and SF in vivo may deleteriously affect the stem cell compartment, while expanding terminal myelopoiesis. Human clonogenic progenitors are more prevalent in the blood of the transplanted growth factor-producing mice and this is accompanied by a very marked reduction of more primitive human cells in the BM. This phenotype is characterized by an enhancement of terminal human myelopoiesis and a matched suppression of terminal human erythropoiesis, with a slight reduction in human B-lymphopoiesis in the BM of the engrafted mice. Here, we show that nonobese diabetic severe combined immunodeficiency mice genetically engineered to produce ng/ml serum levels of human interleukin-3 (IL-3), granulocyte/macrophage-stimulating factor (GM-CSF) and Steel factor (SF) display a complex phenotype when transplanted with primitive human bone marrow (BM) or fetal liver cells. In contrast, the effects of continuous exposure to such molecules have not been well investigated. These include demonstration of the ability of injected ‘human-specific’ hematopoietic growth factors to enhance the production of human cells at multiple levels of differentiation. Transplantation of immunodeficient mice with human hematopoietic cells has greatly facilitated studies of the earliest stages of human hematopoiesis.
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