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.
Highlights
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders with diverse phenotypes, characterized mainly by ineffective hematopoiesis and bone marrow (BM) morphological dysplasia.1–3 The phenotypic heterogeneity and the highly variable prognosis of MDS patients make it difficult to classify the disease subtype and predict the survival as well as likelihood of transformation to leukemia
We have tested the engraftment potential of MDS in NSG and/or NSG-S immunodeficient mouse models
After 18 weeks, engraftment levels based on human CD45+ cells harvested from engrafted mice ranged between 0.01 and 15%
Summary
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders with diverse phenotypes, characterized mainly by ineffective hematopoiesis and bone marrow (BM) morphological dysplasia.1–3 The phenotypic heterogeneity and the highly variable prognosis of MDS patients make it difficult to classify the disease subtype and predict the survival as well as likelihood of transformation to leukemia. We decided to determine whether patient-derived MSCs can help to improve the engraftment of MDS BM cells in NSG as well as in NSG-S mice as has been previously suggested.11,13 Our results obtained from mice that were injected with 1 × 106 patient MNCs (CD3+ depleted cells) along with 0.5 × 106 MSCs (autologous or allogeneic) did not show any improvement in engraftment levels in both mouse models (Figure 1c).
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