Preclinical modeling of myelodysplastic syndromes

骨髓增生异常综合征的临床前建模

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作者:K Rouault-Pierre, S A Mian, M Goulard, A Abarrategi, A Di Tulio, A E Smith, A Mohamedali, S Best, A-M Nloga, A G Kulasekararaj, L Ades, C Chomienne, P Fenaux, C Dosquet, G J Mufti, D Bonnet

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.

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