Back to Search
Start Over
Mesenchymal stromal cells from myelodysplastic and acute myeloid leukemia patients display in vitro reduced proliferative potential and similar capacity to support leukemia cell survival
- Source :
- Stem Cell Research & Therapy, Stem Cell Research & Therapy, Vol 9, Iss 1, Pp 1-15 (2018)
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Background Mesenchymal 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. Methods We 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). Results We 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. Conclusions Overall, 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.
- Subjects :
- Male
0301 basic medicine
Cell
Mesenchymal stromal cells
Gene Expression
Medicine (miscellaneous)
0302 clinical medicine
hemic and lymphatic diseases
lcsh:QD415-436
In Situ Hybridization, Fluorescence
Aged, 80 and over
lcsh:R5-920
Mesenchymal stromal cell
Myeloid leukemia
Cell Differentiation
Middle Aged
Hematopoietic stem cell proliferation
Neoplasm Proteins
Leukemia, Myeloid, Acute
Leukemia
medicine.anatomical_structure
Molecular Medicine
Female
Stem cell
lcsh:Medicine (General)
Adult
Risk
Adolescent
Cell Survival
Primary Cell Culture
Biology
Biochemistry, Genetics and Molecular Biology (miscellaneous)
lcsh:Biochemistry
03 medical and health sciences
Biomarkers, Tumor
medicine
Humans
Leukemic microenvironment
Aged
Cell Proliferation
Acute myeloid leukemia
Research
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
medicine.disease
Molecular medicine
030104 developmental biology
Case-Control Studies
Myelodysplastic Syndromes
Cancer research
Bone marrow
Myelodysplastic syndrome
030215 immunology
Subjects
Details
- ISSN :
- 17576512
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....cecd6fffb3e72457dcdd226fa563253c