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Assessing the Mechanisms of MDS and Its Transformation to Leukemia in a Novel Humanized Mouse

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Technical Report,15 Aug 2013,14 Feb 2016

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Yale University New Haven United States

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The overall goal of this project is to develop a model for the study of myelodysplasia MDS, an acquired bone marrow failure syndrome in the aging population and in cancer survivors. MDS is inherently difficult to study. MDS stem cells cannot be grown in culture and in vivo models are thus the gold standard. However, MDS stem cells are diseased and fail to efficiently engraft in current immunodeficient mouse models. We have optimized engraftment of normal adult HSPC into MISTRG. We have determined optimal cell preparation, cell number, pre-engraftment irradiation dose, transplantation route and recipient age. We have optimized the analysis of engrafted humanized mice. We have successfully transplanted primary MDS bone marrow cells into MISTRG mice with successful engraftment and replication of the donor disease status. We have successfully performed secondary transplantation of MDS BM cells to propagate human MDS in MISTRG mice for therapeutic testing.

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