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Preclinical modeling of myelodysplastic syndromes

Rouault-Pierre, K; Mian, SA; Goulard, M; Abarrategi, A; Di Tulio, A; Smith, AE; Mohamedali, A; ... Bonnet, D; + view all (2017) Preclinical modeling of myelodysplastic syndromes. Leukemia , 31 (12) pp. 2702-2708. 10.1038/leu.2017.172. Green open access

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Abstract

Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematological clonal disorders. Here, we have tested the bone marrow (BM) cells from 38 MDS patients covering all risk groups in two immunodeficient mouse models: NSG and NSG-S. Our data show comparable level of engraftment in both models. The level of engraftment was patient specific with no correlation to any specific MDS risk group. Furthermore, the co-injection of mesenchymal stromal cells (MSCs) did not improve the level of engraftment. Finally, we have developed an in vitro two-dimensional co-culture system as an alternative tool to in vivo. Using our in vitro system, we have been able to co-culture CD34+cells from MDS patient BM on auto- and/or allogeneic MSCs over 4 weeks with a fold expansion of up to 600 times. More importantly, these expanded cells conserved their MDS clonal architecture as well as genomic integrity.

Type: Article
Title: Preclinical modeling of myelodysplastic syndromes
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/leu.2017.172
Publisher version: https://doi.org/10.1038/leu.2017.172
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/ by/4.0/
Keywords: Animals, Biomarkers, Bone Marrow Cells, Bone Marrow Transplantation, Chromosome Aberrations, Disease Models, Animal, Female, Gene Expression, Genes, Reporter, Heterografts, Humans, Immunophenotyping, Male, Mesenchymal Stromal Cells, Mice, Mice, Knockout, Myelodysplastic Syndromes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10045750
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