Mesenchymal stem cells in myelodysplastic syndromes: phenotypic and cytogenetic characterization

Bone marrow-derived mesenchymal stem cells (MSC) have been defined as primitive, undifferentiated cells, capable of self-renewal and with the ability to give rise to different cell lineages, including adipocytes, osteocytes, fibroblasts, chondrocytes, and myoblasts. MSC are key components of the hematopoietic microenvironment. Several studies, including some from our own group, suggest that important quantitative and functional alterations are present in the stroma of patients with myelodysplasia (MDS). However, in most of such studies the stroma has been analyzed as a complex network of different cell types and molecules, thus it has been difficult to identify and characterize the cell(s) type(s) that is (are) altered in MDS. In the present study, we have focused on the biological characterization of MSC from MDS. As a first approach, we have quantified their numbers in bone marrow, and have worked on their phenotypic (morphology and immunophenotype) and cytogenetic properties. MSC were obtained by a negative selection procedure and cultured in a MSC liquid culture medium. In terms of morphology, as well as the expression of certain cell markers, no differences were observed between MSC from MDS patients and those derived from normal marrow. In both cases, MSC expressed CD29, CD90, CD105 and Prolyl-4-hydroxylase; in contrast, they did not express CD14, CD34, CD68, or alkaline phosphatase. Interestingly, in five out of nine MDS patients, MSC developed in culture showed cytogenetic abnormalities, usually involving the loss of chromosomal material. All those five cases also showed cytogenetic abnormalities in their hematopoietic cells. Interestingly, in some cases there was a complete lack of overlap between the karyotypes of hematopoietic cells and MSC. To the best of our knowledge, the present study is the first in which a pure population of MSC from MDS patients is analyzed in terms of their whole karyotype and demonstrates that in a significant proportion of patients, MSC are cytogenetically abnormal. Although the reason of this is still unclear, such alterations may have an impact on the physiology of these cells. Further studies are needed to assess the functional integrity of MDS-derived MSC.