Graphical The road map of MSC review.

Background: MicroRNAs (miRNAs) are small (19-22-nt) single-stranded noncoding RNA molecules whose deregulation of expression can contribute to human disease including the multistep processes of carcinogenesis in human. Circulating miRNAs are emerging biomarkers in many diseases and cancers such as type 2 diabetes, pulmonary disease, colorectal cancer, and gastric cancer among others; however, defining a plasma miRNA signature in acute myeloblastic leukemia (AML) that could serve as a biomarker for diagnosis or in the follow-up has not been done yet. Methods: TaqMan miRNA microarray was performed to identify deregulated miRNAs in the plasma of AML patients. Quantitative real-time RT-PCR was used to validate the results. Receiver-operator characteristic (ROC) curve analysis was conducted to evaluate the diagnostic accuracy of the highly and significantly identified deregulated miRNA(s) as potential candidate biomarker(s). Results: The plasma expression level of let-7d, miR-150, miR-339, and miR-342 was down-regulated whilst that of let-7b, and miR-523 was up-regulated in the AML group at diagnosis compared to healthy controls. ROC curve analyses revealed an AUC (the areas under the ROC curve) of 0.835 (95% CI: 0.7119– 0.9581; P<0.0001) and 0.8125 (95% CI: 0.6796–0.9454; P=0.0005) for miR-150, and miR-342 respectively. Combined ROC analyses using these 2 miRNAs revealed an elevated AUC of 0.86 (95% CI: 0.7819–0.94; P<0.0001) indicating the additive effect in the diagnostic value of these 2 miRNAs. QRT-PCR results showed that the expression level of these two miRs in complete remission AML patients resembled that of healthy controls. Conclusions: Our findings indicated that plasma miR-150 and miR-342 are novel important promising biomarkers in the diagnosis of AML. These novel and promising markers warrant validation in larger prospective studies.

Mesenchymal stromal cells (MSCs) possess immunomodulatory functions and have been proposed as a tool for managing or preventing graft-versus-host disease. Recently, adipose tissue (AT) and Wharton's jelly (WJ) have been reported as potential alternative MSC sources to bone marrow (BM). In this study, we investigated the capacity of MSCs derived from AT and WJ to modulate lymphocyte proliferation as well as their impact on regulatory T-cells. We also evaluated MSC expression of leukemia inhibitory factor and the role of this molecule in the mechanism of MSC-mediated inhibition. We demonstrated that WJ- and AT-MSCs induced a dose-dependent inhibition of T-cell proliferation regardless of the stimuli used to activate T-cells. WJ- and AT-MSCs were more potent than BM-MSCs in suppressing lymphocyte responses, and they mediated this effect by secreting high levels of leukemia inhibitory factor. We also observed that WJ- and AT-MSCs maintained and promoted the expansion of regulatory T-cells independently of the MSC/T-cell ratio. Because human WJ and AT contain MSCs with potent immunomodulatory capacities, they could represent an alternative to BM. Using WJ- and AT-MSCs in clinical therapies, such as the prevention and/or reduction of graft-versus-host disease and in the treatment of autoimmune diseases, is particularly promising. Further characterization of MSC physiological functions will increase the safety and efficacy of their use in clinical settings.