Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice
- 1 December 2000
- journal article
- research article
- Published by Springer Science and Business Media LLC in Bone Marrow Transplantation
- Vol. 26 (11), 1211-1216
- https://doi.org/10.1038/sj.bmt.1702702
Abstract
The scid mutation was backcrossed on to the NOD/Shi mouse background, resulting in the development of NOD/Shi-scid mice, which showed lack of mature lymphocytes, macrophage dysfunction and absence of circulating complement, but were not as impaired in natural killer (NK) cell activity as NOD/LtSz-scid mice. We then examined the effect of recipient NK cell depletion by anti-asialo GM1 antiserum on the repopulation of human cord blood (CB) hematopoietic stem cells (HSC) in NOD/Shi-scid mice to clarify the role of recipient NK cells in human HSC engraftment. The anti-asialo GM1 antiserum treatment significantly enhanced the engraftment of CB CD34+ cells, but did not affect the differentiation of the engrafted HSC into each hematopoietic lineage. The NK cell depletion was effective at early stages of the engraftment, but not 3 weeks after the transplantation. The anti-asialo GM1 antiserum treatment did not improve the engraftment by human HSC in scid mice which lack mature lymphocytes, but show neither macrophage dysfunction nor a reduction in circulating complement, indicating that macrophages and/or complement also have roles in HSC graft rejection. The present study indicates that the preconditioning targeting of recipient NK cells in addition to T cell suppression and myeloablation might prevent HSC graft failure, and that NOD/Shi-scidmice treated with anti-asialo GM1 antiserum could provide a useful tool for evaluating the repopulating ability of transplantable human HSC. Bone Marrow Transplantation (2000) 26, 1211–1216.Keywords
This publication has 17 references indexed in Scilit:
- Expansion of human NOD/SCID-repopulating cells by stem cell factor, Flk2/Flt3 ligand, thrombopoietin, IL-6, and soluble IL-6 receptorJCI Insight, 2000
- Improved engraftment of human hematopoietic cells in severe combined immunodeficient (SCID) mice carrying human cytokine transgenes.The Journal of Experimental Medicine, 1995
- Engraftment of immune-deficient mice with primitive hematopoietic cells from β-thalassemia and sickle cell anemia patients: implications for evaluating human gene therapy protocolsHuman Molecular Genetics, 1995
- Murine Natural Killer Cells and Marrow Graft RejectionAnnual Review of Immunology, 1992
- Engraftment and long-term expression of human fetal hemopoietic stem cells in sheep following transplantation in utero.JCI Insight, 1992
- Cytokine Stimulation of Multilineage Hematopoiesis from Immature Human Cells Engrafted in SCID MiceScience, 1992
- Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen.The Journal of Experimental Medicine, 1990
- Purification and Characterization of Mouse Hematopoietic Stem CellsScience, 1988
- Mechanisms of Early Allogeneic Marrow Graft Rejection*Immunological Reviews, 1983
- A severe combined immunodeficiency mutation in the mouseNature, 1983