A highly efficient and faithful MDS patient-derived xenotransplantation model for pre-clinical studies View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Yuanbin Song, Anthony Rongvaux, Ashley Taylor, Tingting Jiang, Toma Tebaldi, Kunthavai Balasubramanian, Arun Bagale, Yunus Kasim Terzi, Rana Gbyli, Xiaman Wang, Xiaoying Fu, Yimeng Gao, Jun Zhao, Nikolai Podoltsev, Mina Xu, Natalia Neparidze, Ellice Wong, Richard Torres, Emanuela M. Bruscia, Yuval Kluger, Markus G. Manz, Richard A. Flavell, Stephanie Halene

ABSTRACT

Comprehensive preclinical studies of Myelodysplastic Syndromes (MDS) have been elusive due to limited ability of MDS stem cells to engraft current immunodeficient murine hosts. Here we report a MDS patient-derived xenotransplantation model in cytokine-humanized immunodeficient "MISTRG" mice that provides efficient and faithful disease representation across all MDS subtypes. MISTRG MDS patient-derived xenografts (PDX) reproduce patients' dysplastic morphology with multi-lineage representation, including erythro- and megakaryopoiesis. MISTRG MDS-PDX replicate the original sample's genetic complexity and can be propagated via serial transplantation. MISTRG MDS-PDX demonstrate the cytotoxic and differentiation potential of targeted therapeutics providing superior readouts of drug mechanism of action and therapeutic efficacy. Physiologic humanization of the hematopoietic stem cell niche proves critical to MDS stem cell propagation and function in vivo. The MISTRG MDS-PDX model opens novel avenues of research and long-awaited opportunities in MDS research. More... »

PAGES

366

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-08166-x

    DOI

    http://dx.doi.org/10.1038/s41467-018-08166-x

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111563893

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30664659


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