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LY86, LRG1 and PDE9A genes overexpression in umbilical cord blood hematopoietic stem progenitor cells by acute myeloid leukemia (M3) microvesicles.

ABSTRACT: Background:Microvesicles as a new device of cell-cell communication are potentially able to induce some phenotypes and genotypes of an origin cell in a target cell. We evaluate the role of leukemia microvesicles on the leukemia stem cells (LSCs)-specific genes expression in healthy hematopoietic stem progenitor cells (HSPCs). Methods:HL-60 and NB-4 cell lines were selected for microvesicles isolation by ultracentrifugation. Healthy HSPCs were obtained by magnetic association cell sorting (MACS) and CD-34 micro-beads from umbilical cord blood samples and then, were treated with 20 and 40 ?g/ml leukemia microvesicles for 10 days, respectively. LY86, LRG1 and PDE9A genes expression as LSC specific genes were analyzed by QRT-PCR. Surface CD-34 antigen as stemness marker was measured by flow cytometry technique. Results:Healthy HSPCs showed a significant increase in LSC specific genes expression after treatment with both 20 and 40 ?g/ml leukemia microvesicles at day 10. All studied groups showed more than 70% surface CD-34 antigen at the last day of experiment which proved HSPCs stemness. Conclusion:Our results suggest that healthy HSPCs can be transformed genetically by leukemia microvesicles to over express LSC specific genes. This may be further evidence of leukemia-like transformation by leukemia microvesicles.

SUBMITTER: Razmkhah F

PROVIDER: S-EPMC6751795 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro.

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| S-EPMC8036704 | biostudies-literature

Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation.

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Project description:We performed m6A-seq analysis with CD34+ human umblilical cord blood HSPCs

2018-08-17 | GSE107954 | GEO

Ex Vivo Expansion of CD34+ CD90+ CD49f+ Hematopoietic Stem and Progenitor Cells from Non-Enriched Umbilical Cord Blood with Azole Compounds.

Project description:Umbilical cord blood (UCB) transplants in adults have slower hematopoietic recovery compared to bone marrow (BM) or peripheral blood (PB) stem cells mainly due to low number of total nucleated cells and hematopoietic stem and progenitor cells (HSPC). As such in this study, we aimed to perform ex vivo expansion of UCB HSPC from non-enriched mononucleated cells (MNC) using novel azole-based small molecules. Freshly-thawed UCB-MNC were cultured in expansion medium supplemented with small molecules and basal cytokine cocktail. The effects of the expansion protocol were measured based on in vitro and in vivo assays. The proprietary library of >50 small molecules were developed using structure-activity-relationship studies of SB203580, a known p38-MAPK inhibitor. A particular analog, C7, resulted in 1,554.1?±?27.8-fold increase of absolute viable CD45+ CD34+ CD38- CD45RA- progenitors which was at least 3.7-fold higher than control cultures (p?<?.001). In depth phenotypic analysis revealed >600-fold expansion of CD34+ /CD90+ /CD49f+ rare HSPCs coupled with significant (p?<?.01) increase of functional colonies from C7 treated cells. Transplantation of C7 expanded UCB grafts to immunodeficient mice resulted in significantly (p?<?.001) higher engraftment of human CD45+ and CD45+ CD34+ cells in the PB and BM by day 21 compared to non-expanded and cytokine expanded grafts. The C7 expanded grafts maintained long-term human multilineage chimerism in the BM of primary recipients with sustained human CD45 cell engraftment in secondary recipients. In conclusion, a small molecule, C7, could allow for clinical development of expanded UCB grafts without pre-culture stem cell enrichment that maintains in vitro and in vivo functionality. Stem Cells Translational Medicine 2018;7:376-393.

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Human Mesenchymal Stem/Stromal Cells from Umbilical Cord Blood and Placenta Exhibit Similar Capacities to Promote Expansion of Hematopoietic Progenitor Cells In Vitro.

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Project description:Late outgrowth endothelial progenitor cells (EPCs) represent a promising cell source for rapid reendothelialization of damaged vasculature after expansion ex vivo and injection into the bloodstream. We characterized the dynamic adhesion of umbilical-cord-blood-derived EPCs (CB-EPCs) to surfaces coated with fibronectin. CB-EPC solution density affected the number of adherent cells and larger cells preferentially adhered at lower cell densities. The number of adherent cells varied with shear stress, with the maximum number of adherent cells and the shear stress at maximum adhesion depending upon fluid viscosity. CB-EPCs underwent limited rolling, transiently tethering for short distances before firm arrest. Immediately before arrest, the instantaneous velocity decreased independent of shear stress. A dimensional analysis indicated that adhesion was a function of the net force on the cells, the ratio of cell diffusion to sliding speed, and molecular diffusivity. Adhesion was not limited by the settling rate and was highly specific to ?(5)?(1) integrin. Total internal reflection fluorescence microscopy showed that CB-EPCs produced multiple contacts of ?(5)?(1) with the surface and the contact area grew during the first 20 min of attachment. These results demonstrate that CB-EPC adhesion from blood can occur under physiological levels of shear stress.

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