Mesenchymal stromal cells from myelodysplastic and acute myeloid leukemia patients display in vitro reduced proliferative potential and similar capacity to support leukemia cell survival

Abstract

BackgroundMesenchymal stromal cells (MSCs) are an essential element of the bone marrow (BM) microenvironment, playing a crucial function in regulating hematopoietic stem cell proliferation and differentiation. Recent findings have outlined a putative role for MSCs in hematological malignancy development. So far, conflicting results have been collected concerning MSC abnormalities in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In particular, a considerable amount of evidence has been accumulated strongly supporting a permissive role of MSCs in malignancy evolution to MDS, while a potentially causative or promoting function performed by MSCs in AML has not yet been fully clarified. Here, we compared MSCs isolated from healthy, MDS, and AML subjects to investigate MSC alterations and to emphasize putative common and/or diverse features.MethodsWe isolated and expanded MSCs from AML patients (AML-MSCs) and MDS patients (MDS-MSCs), and we analyzed and compared their phenotypic and functional properties with respect to each other and versus healthy donor-derived MSCs (HD-MSCs).ResultsWe found that stable MSC cultures could be easily established from HD and MDS mononuclear BM-derived cells, while a substantial fraction (25%) of AML patients failed to yield MSCs. Nevertheless, isolated MDS-MSCs and AML-MSCs, as well as HD-MSCs, contained the basic features of MSCs. Indeed, they displayed similar surface marker expression and efficient capacity to differentiate versus osteogenic and adipogenic lineage in vitro. We also proved that MDS-MSCs and AML-MSCs, analyzed by fluorescence in-situ hybridization, did not harbor leukemic cell cytogenetic abnormalities. Moreover, MDS-MSCs and AML-MSCs were similar in terms of ability to sustain AML cell viability and immune-regulatory capacity. However, we were also able to detect some differences between AML-MSCs and MDS-MSCs. Indeed, we found that the frequency of rescued MSCs was lower in the AML group than in the HD and MDS groups, suggesting that a reduced number of MSC precursors could inhabit AML BM. Instead, MDS-MSCs showed the lowest proliferative capacity, reflecting some intrinsic and particular defect.ConclusionsOverall, our results elucidated that MDS-MSCs and AML-MSCs did not show macroscopic and/or tumor-related defects, but both displayed functional features potentially contributing to favor a leukemia-protective milieu.

Bone marrow mesenchymal stromal cells from acute myelogenous leukemia patients demonstrate adipogenic differentiation propensity with implications for leukemia cell support

“…Others have shown that AML-MSCs vs. ND-MSCs had decreased ability to support normal cobblestone area forming cells [56]. Other groups found no difference between AML-MSCs and ND-MSCs to support normal hematopoiesis in vitro [57]. Likewise, in this work, it was shown that AML-MSCs supported CFU-GMs more robustly that did ND-MSCs, but differential effects on blast apoptosis and survival were not demonstrated.…”

Mesenchymal stromal cells shape the MDS microenvironment by inducing suppressive monocytes that dampen NK cell function

“…Conversely, they may activate the innate and adaptive immune system (4,5). Studies have shown that MSCs undergo molecular and genetic changes contributing to disease progression (6). Other studies failed to show functional differences between MSCs from patients with MDS (MDS-MSCs) and healthy individuals (7,8).…”

Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma

“…Studies have shown that patient's BM‐MSCs do not harbour the same genetic abnormalities present in malignant cells. Common or disease‐specific genetic alteration in haematologic malignancies has not been identified 2‐5 . BM‐MSCs from patients with myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) exhibit a wide range of functional and molecular alterations 4,6 .…”