Preclinical modeling of myelodysplastic syndromes
journal contributionposted 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.
AnimalsBiomarkersBone Marrow CellsBone Marrow TransplantationChromosome AberrationsDisease Models, AnimalFemaleGene ExpressionGenes, ReporterHeterograftsHumansImmunophenotypingMaleMesenchymal Stem CellsMiceMice, KnockoutMyelodysplastic SyndromesMesenchymal Stromal CellsBonnet FC001045BRF-ackFC-ackImmunology1103 Clinical Sciences1112 Oncology and Carcinogenesis