Alterations of Multipotent Mesenchymal Stromal Cells Induced by Interaction with Allogeneic Lymphocytes In Vitro

Multipotent mesenchymal stromal cells (MSCs) are widely used for cell therapy. Treatment with interferon-γ (IFNγ) increases the immunomodulating properties of MSCs. When administered intravenously, MSCs interact with lymphocytes. It is impossible to follow the fate of MSCs in the recipient organism. The aim of this study was to investigate the properties of MSCs after their interaction with lymphocytes in vitro. Bone marrow MSCs were co-cultured for 4 days with activated and non-activated lymphocytes. A portion of the MSCs was pretreated with IFNγ. HLA-DR expression on the MSCs increased when these cells were co-cultured with lymphocytes and after they were treated with IFNγ. The activated lymphocytes induced significantly higher HLA-DR expression levels than did IFNγ treatment. IFNγ increased the viability of MSCs when these cells were co-cultured with lymphocytes. The immunomodulating properties of MSCs were amplified after IFNγ priming and co-cultivation with lymphocytes; therefore, this amplification was not dependent on the IFNγ source. IFNγ treatment and lymphocyte interactions induced increases in the relative expression levels (RELs) of ICAM1 and factors involved in immunomodulation in the MSCs. IFNγ stabilizes MSCs while maintaining their viability. The data suggest that MSCs obtained from the hematopoietic cells donor or autologous should be used for cell therapy

Deletions of specific exons of FHOD3 detected by next-generation-sequencing are associated with hypertrophic cardiomyopathy

Despite new strategies, such as evaluating deep intronic variants and new genes in whole-genome-sequencing studies, the diagnostic yield of genetic testing in hypertrophic cardiomyopathy (HCM) is still around 50%. FHOD3 has emerged as a novel disease-causing gene for this phenotype, but the relevance and clinical implication of copy-number-variations (CNVs) have not been determined. In this study, CNVs were evaluated using a comparative depth-of-coverage strategy by NGS in 5493 hypertrophic cardiomyopathy probands and 2973 disease-controls. We detected three symmetrical deletions in FHOD3 that involved exons 15 and 16 in three HCM families (no CNVs were detected in the control group). These exons are part of the diaphanous inhibitory domain of FHOD3 protein, considered a cluster of mutations for HCM. The clinical characteristics of the affected carriers were consistent with those reported in FHOD3 in previous studies. This study highlights the importance of performing CNV analysis systematically in NGS genetic testing panels for HCM, and reinforce the relevance of the FHOD3 gene in the disease. This article is protected by copyright. All rights reserved

Multipotent Mesenchymal Stromal Cells Derived from the Bone Marrow Transported Over 12 Hours Change Their Main Characteristics

Many investigations have addressed the possibility of using multipotent mesenchymal stromal cells (MSCs) for treatment of various diseases due to their ability for tissue regeneration and unique immunomodulating capacities. These stromal cells can be cultivated in vitro and represent adult, fibroblast-like cells that can differentiate into tissues of mesodermal origin. Previous studies have attempted to develop the criteria for human MSC eligibility for therapeutic applications. MSCs secrete various cytokines, growth factors and extracellular matrix molecule