Preclinical modeling of myelodysplastic syndromes

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

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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.

Original languageEnglish
Pages (from-to)2702-2708
Number of pages7
JournalLeukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Volume31
Issue number12
Early online date2 Jun 2017
DOIs
Publication statusPublished - 1 Dec 2017

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