Search results for "Haematopoiesi"
showing 10 items of 183 documents
Ex vivo expansion of umbilical cord blood (UCB) CD34+ cells alters the expression and function of α4β1 and α5β1 integrins
2001
We have investigated the influence of ex vivo expansion of human CD34+ cord blood cells on the expression and function of adhesion molecules involved in the homing and engraftment of haematopoietic progenitors. Ex vivo expansion of umbilical cord blood CD34+ cells for 6 d in the presence of interleukin 3 (IL-3), IL-6 and stem cell factor (SCF) or IL-11, SCF and Flt-3L resulted in increased expression of α4, α5, β1, αΜM and β2 integrins. However, a significant decrease in the adhesion of progenitor cells to fibronectin was observed after the ex vivo culture (adhesion of granulocyte-macrophage colony-forming units (CFU-GM) was 22 ± 4% in fresh cells versus 5 ± 2% and 2 ± 2% in each combinatio…
EPCR Signaling Controls the Activity of Hematopoietic Stem Cells Independent of Coagulation Regulation
2021
Abstract Background All mature blood cells are derived from multipotent hematopoietic stem cells (HSCs) which are activated to meet the demand of the host during inflammation and injury. The endothelial cell protein C receptor (EPCR) is a marker for primitivity and quiescence of HSCs but the relative contributions of EPCR signaling versus anticoagulant functions in HSC maintenance are incompletely defined. Aims We aimed to dissect functions of EPCR by studying anticoagulant and signaling function in HSC of EPCR C/S mice carrying a single intracellular point mutation abolishing normal trafficking of EPCR through endo-lysosomal compartments. We assessed the contributions of EPCR signaling to …
Direct Toll-Like Receptor-Mediated Stimulation of Hematopoietic Stem and Progenitor Cells Occurs In Vivo and Promotes Differentiation Toward Macropha…
2012
Abstract As Toll-like receptors (TLRs) are expressed by hematopoietic stem and progenitor cells (HSPCs), they may play a role in hematopoiesis in response to pathogens during infection. We show here that TLR2, TLR4, and TLR9 agonists (tripalmitoyl-S-glyceryl-L-Cys-Ser-(Lys)4 [Pam3CSK4], lipopolysaccharide [LPS], and CpG oligodeoxynucleotide [ODN]) induce the in vitro differentiation of purified murine lineage negative cells (Lin−) as well as HSPCs (identified as Lin− c-Kit+ Sca-1+ IL-7Rα− [LKS] cells) toward macrophages (Mph), through a myeloid differentiation factor 88 (MyD88)-dependent pathway. In order to investigate the possible direct interaction of soluble microorganism-associated mol…
Manganese effects on haematopoietic cells and circulating coelomocytes of Asterias rubens (Linnaeus)
2008
Abstract Manganese (Mn) is a naturally abundant metal in marine sediments where it mainly occurs as MnO 2 . During hypoxic conditions it is converted into a bioavailable state, Mn 2+ , and can reach levels that previously have shown effects on immune competent cells of the crustacean, Nephrops norvegicus . Here we investigated if Mn also affects circulating coelomocytes and their renewal in the common sea star, Asterias rubens , when exposed to concentrations of Mn that can be found in nature. When the sea stars were exposed to Mn it accumulated in the coelomic fluid and the number of circulating coelomocytes, in contrast to what was recorded in Nephrops , increased significantly. By using …
Gene expression of stem cells at different stages of ontological human development.
2013
Abstract Objectives To compare multipotent mesenchymal stem cells (MSCs) obtained from chorionic villi (CV), amniotic fluid (AF) and placenta, with regard to their phenotype and gene expression, in order to understand if MSCs derived from different extra-embryonic tissues, at different stages of human ontological development, present distinct stemness characteristics. Study design MSCs obtained from 30 samples of CV, 30 of AF and 10 placentas (obtained from elective caesarean sections) were compared. MSCs at second confluence cultures were characterized by immunophenotypic analysis with flow cytometry using FACS CANTO II. The expression of the genes Oct-4 (Octamer-binding transcription fact…
The Challenge of Using CB-HSCs As Source for Gene Therapy: Lentiviral Vector Transduction, Phenotypic Characterization and Global Gene Expression Pro…
2015
Abstract Introduction: Genetic modification of autologous hematopoietic stem and progenitor cells (HSPC) is a promising clinical intervention to cure inherited monogenic diseases. Successful gene therapy trials have already been conducted using CD34+ cells from bone marrow and from mobilized peripheral blood. In this regard, cord blood (CB) represents an attractive source of HSCs due to its high concentration of high proliferative HSPC and increased susceptibility to be transduced by lentiviral vectors. Unfortunately, the major disadvantage is the limited number of HSC in the CB collection. Consequently, ex-vivo expansion of CB-HSC is desirable to extend clinical applications. Purposes: To …
EPCR/PAR1 Signaling Navigates Long-Term Repopulating Hematopoietic Stem Cell Bone Marrow Homing to Thrombomodulin-Enriched Blood Vessels
2015
Abstract Bone marrow (BM) homing and lodgment of long-term repopulating hematopoietic stem cells (LT-HSCs) is an active and essential first step in clinical stem cell transplantation. EPCR is expressed by murine BM LT-HSCs endowed with the highest repopulation potential and its ligand, activated protein C (aPC), has anticoagulant and anti-sepsis effects in EPCR+/PAR1+ endothelial cells. We recently found that signaling cascades, traditionally viewed as coagulation and inflammation related, also independently control EPCR+ LT-HSC BM retention and recruitment to the blood via distinct PAR1 mediated pathways. EPCR/PAR1 signaling retains LT-HSCs in the BM by restricting nitric oxide (NO) produc…
Demonstration of a Role for Dot1l In MLL-Rearranged Leukemia Using a Conditional Loss of Function Model
2010
Abstract Abstract 62 Leukemias associated with translocations of the Mixed Lineage Leukemia (MLL) gene account for a significant percentage of both AML and ALL, and often carry a poor prognosis. The exact molecular mechanisms by which MLL-fusion proteins transform cells are incompletely understood. One proposed model involves the aberrant activation of transcriptional programs through epigenetic changes that ultimately lead to leukemogenesis. The histone 3 lysine 79 (H3K79) methyltransferase Dot1l has been shown to be recruited by the most common MLL fusion proteins, and MLL fusion protein target loci are associated with H3K79 methylation (H3K79me2/3) in mouse models and MLL-rearranged huma…
Clinical virology of cytomegalovirus infection following hematopoietic transplantation
2010
Cytomegalovirus (CMV) causes significant morbidity and mortality in allogeneic stem cell transplant recipients. The incidence of early CMV disease has been dramatically reduced by use of preemptive therapeutic strategies. Nevertheless, a trend toward a later appearance of CMV disease is being increasingly recognized. Currently, quantitative real-time PCR assays are the first-line choice for monitoring active CMV infection. However, no threshold DNAemia levels for triggering the initiation of preemptive therapy have been clinically validated in large studies. Although more time limited than universal prophylaxis, preemptive therapy strategies may also result in over treatment. Combined viro…
Alteration of HSC Functions in Thalassemia
2015
Abstract Beta-thalassemia represents one of the most globally widespread monogenic disorders and is characterized by significantly reduced or absent synthesis of hemoglobin beta-chains. In its severe form the insufficient production of adult hemoglobin results in altered erythropoiesis, hemolytic anemia, bone marrow (BM) hematopoietic hyperplasia and splenomegaly often associated with extramedullary hematopoiesis, requiring regular blood transfusions and iron chelation treatment. Over the last two decades many progresses were made in the field of allogeneic bone marrow (BM) transplantation to definitively cure beta-thalassemia. In parallel, experimental autologous transplantation protocols …