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Murine Models

Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice

Bone Marrow Transplantation volume 26, pages 1211–1216 (2000)Cite this article

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.

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Acknowledgements

This study was supported by the Program for Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research of Japan.

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Authors and Affiliations

  1. Department of Clinical Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    H Yoshino, T Ueda, Y Ebihara, A Manabe, R Tanaka, S Asano & K Tsuji

  2. Department of Pediatrics, Kyorin University School of Medicine, Tokyo, Japan

    H Yoshino

  3. Central Institute for Experimental Animals, Kawasaki, Japan

    M Kawahata, K Kobayashi & M Ito

  4. Department of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    S Asano

  5. Department of Pediatrics, Kyoto University, Kyoto, Japan

    T Nakahata

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  1. H Yoshino
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Yoshino, H., Ueda, T., Kawahata, M. et al. Natural killer cell depletion by anti-asialo GM1 antiserum treatment enhances human hematopoietic stem cell engraftment in NOD/Shi-scid mice. Bone Marrow Transplant 26, 1211–1216 (2000). https://doi.org/10.1038/sj.bmt.1702702

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  • DOI: https://doi.org/10.1038/sj.bmt.1702702

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