In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton’s jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population. MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs. Both ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs. Overall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications.

In the present study we explore the extracellular matrix (ECM) produced by human bone marrow mesenchymal stem/stromal cells (BM-MSCs) induced to undergo osteogenic differentiation within porous chitosan/gelatin (CS:Gel) scaffolds by investigating their multiple gene expression profile and mechanical behavior. Initially, the efficiency of the BM-MSCs osteogenic differentiation within the constructs was confirmed by the significant rise in the expression of the osteogenesis associated genes DLX5, RUNX2, ALP and OSC . In line with these findings, OSC and Col1A1 protein expression was also detected in BM-MSCs on the CS:Gel scaffolds at day 14 of osteogenic differentiation. We then profiled, for the first time, the expression of 84 cell adhesion and ECM molecules using PCR arrays. The arrays, which were conducted at day 14 of osteogenic differentiation, demonstrated that 49 genes including collagens, integrins, laminins, ECM proteases, catenins, thrombospondins, ECM protease inhibitors and cell-cell adhesion molecules were differentially expressed in BM-MSCs seeded on scaffolds compared to tissue culture polystyrene control. Moreover, we performed dynamic mechanical analysis of the cell-loaded scaffolds on days 0, 7 and 14 to investigate the correlation between the biological results and the mechanical behavior of the constructs. Our data demonstrate a significant increase in the stiffness of the constructs with storage modulus values of 2 MPa on day 7, compared to 0.5 MPa on day 0, following a drop of the stiffness at 0.8 MPa on day 14, that may be attributed to the significant increase of specific ECM protease gene expression such as MMP1, MMP9, MMP11 and MMP16 at this time period.

Background-Objectives: Although considered standard of care for patients with low-/intermediate-1 risk MDS and isolated del(5q), lenalidomide is not widely used in patients exhibiting additional cytogenetic abnormalities, on top of del(5)q. The aim of this study was to provide real-world evidence for the efficacy of lenalidomide in patients with del(5q), with or without additional cytogenetic abnormalities. Methods: Patients with MDS exhibiting del(5q) in the Greek National Myelodysplastic Syndromes Registry were analyzed if they had received at least one lenalidomide dose and detailed response assessment/follow-up was available. Results: Among 238 patients analyzed, 153 (64.3%) had del(5q) syndrome (Group-I), 34 (14.3%) had an isolated del(5q) abnormality but were not 5q− syndrome (Group-II), 26 (10.9%) had del(5q) plus only one additional cytogenetic abnormality (Group-III), and 25 (10.5%) had del(5q) plus >1 additional abnormality (Group-IV). Among 218 (91.6%) evaluable patients, a major response was achieved by 146 (67.0%) patients, 114/146 (78.1%) in Group-I, 18/31 (58.1%) in Group-II, 10/20 (50.0%) in Group-III, and 4/21 (19.0%) in Group-IV. Overall, hematological response was seen in 177/218 (81.2%) patients, even among those with an excess of bone marrow blasts/frank acute myeloid leukemia. Duration of response was comparable between the four patient groups. A complete cytogenetic response was achieved by 38.0% overall, more commonly in Group-I (42.3%) and -III (35.7%). Transfusion-independent patients and those with a higher MCV or lower marrow blast cells at baseline had a higher probability of achieving a major response. With multivariate analysis, factors associated with overall survival were age, performance status, transfusion dependence, and marrow blast cell percentage at treatment start, as well as time from initial diagnosis to lenalidomide start. Conclusions: Lenalidomide was highly effective in patients with the del(5)q syndrome and also in those with isolated del(5)q, other than del(5)q syndrome, or those exhibiting del(5)q plus only one additional cytogenetic abnormality, not affecting chromosome 7.