Mesenchymal cells generated from patients with myelodysplastic syndromes are devoid of chromosomal clonal markers and support short- and long-term hematopoiesis in vitro

Abstract

Myelodysplastic syndromes (MDS) are clonal malignant stem cell disorders characterized by inefficient hematopoiesis. The role of the marrow microenvironment in the pathogenesis of the disease has been controversial and no study has been performed so far to characterize mesenchymal cells (MC) from MDS patients and to analyse their ability to support hematopoiesis. To this end, we have isolated and characterized MC at diagnostic marrow samples (n ¼ 12) and have purified their CD34 þ CD38À and CD34 þ CD38 þ counterparts (n ¼ 7) before using MC as a short-and long-term hematopoietic support. We show that MC can be readily isolated from MDS marrow and exhibit a major expansion potential as well as an intact osteoblastic differentiation ability. They do not harbor the abnormal marker identified by FISH in the hematopoietic cells and they stimulate the growth of autologous clonogenic cells. Conversely, highly purified stem cells and their cytokine-expanded progeny harbor the clonal marker with variable frequencies, and both normal and abnormal long-term culture-initiating cell-derived progeny can be effectively supported by autologous MC. Thus, we demonstrate that MDS marrow is an abundant source of MC appearing both cytogenetically and functionally noninvolved by the malignant process and able to support hematopoiesis, suggesting their possible usefulness in future cell therapy approaches.

Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q− syndrome

“…7 Our results support the former data with a lower expansion capacity of MSC from MDS patients. The differences with other reports may be because of the great variability observed among MSC growth in MDS or because cases with absence of growth were not included in the analysis.…”

“…5,6 Nevertheless, the question of whether MSC from MDS patients are abnormal is not clear. Although some groups have reported that MSC display both a normal growth pattern and a normal surface antigen expression as compared with MSC from healthy individuals, [7][8][9] other authors have shown discrepant results. 4,8,10 Even more confusion exists regarding whether or not MSC from MDS display cytogenetic abnormalities.…”

“…Regarding cytogenetic abnormalities, Soenen-Cornu et al 7 have shown that MSC from MDS patients do not harbor the same cytogenetic abnormalities present on their HC counterpart. Nevertheless, other groups have reported the existence of chromosomal aberrations in MSC from MDS.…”

“…4,8,10 Even more confusion exists regarding whether or not MSC from MDS display cytogenetic abnormalities. The studies in this field are scanty and again they show discrepant results from absence of chromosomal markers, 7,11 to the presence of karyotypic aberrations such as hypodiploid cells. 4,8,10 This study aimed to analyze the characteristics of MSC from MDS patients including the growth pattern, the immunophenotype and their cytogenetic characterization by array-based comparative genomic hybridization (array-CGH).…”

Down-regulation of Dicer1 promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells in patients with myelodysplastic syndrome

“…10,13,14 However, other reports suggested that MDS-MSC may have normal support capacity. 11,12,34 The discrepancies in these results might be attributed to differences between patients, cellular populations and experimental protocols in the various studies. Our study also suggested that differences in the cellular senescence of MDS-MSC could contribute to these discrepant results.…”