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Leukemia. 2017 Dec;31(12):2702-2708. doi: 10.1038/leu.2017.172. Epub 2017 Jun 2.

Preclinical modeling of myelodysplastic syndromes.

Author information

1
Haematopoietic Stem Cell Laboratory, The Francis Crick Institute, London, UK.
2
King's College London School of Medicine, Department of Haematological Medicine, London, UK.
3
INSERM, UMRS1131-University Paris Diderot, Saint Louis Hospital, Paris, France.
4
King's College Hospital, Department of Haematology, London, UK.
5
Senior Haematology Department, Saint Louis Hospital, APHP, Paris, France.
6
Cell Biology Department, Saint Louis Hospital, APHP, Paris, France.

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.

PMID:
28663577
PMCID:
PMC5729336
DOI:
10.1038/leu.2017.172
[Indexed for MEDLINE]
Free PMC Article

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