The Francis Crick Institute
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Preclinical modeling of myelodysplastic syndromes

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journal contribution
posted on 2020-10-15, 11:16 authored by K Rouault-Pierre, SA Mian, M Goulard, A Abarrategi, A Di Tulio, AE Smith, A Mohamedali, S Best, A-M Nloga, AG Kulasekararaj, L Ades, C Chomienne, P Fenaux, C Dosquet, GJ Mufti, D Bonnet
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.