Stimulation of β2-adrenergic receptor increases CFTR function and decreases ATP levels in murine hematopoietic stem/progenitor cells.

Background: The chloride channel CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) is expressed by many cell types, including hematopoietic stem/progenitor cells (HSPCs). In this study, we sought to better comprehend the regulation of CFTR activity in HSPCs, namely by beta-adrenergic stimuli.

Methods: The expression of β2-adrenergic receptor (β2-AR) in murine Sca-1(+) HSPCs was investigated by immunofluorescence/confocal microscopy and flow-cytometric analysis.

Hematopoietic and mesenchymal stem cells for the treatment of chronic respiratory diseases: role of plasticity and heterogeneity.

Chronic lung diseases, such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD) are incurable and represent a very high social burden. Stem cell-based treatment may represent a hope for the cure of these diseases. In this paper, we revise the overall knowledge about the plasticity and engraftment of exogenous marrow-derived stem cells into the lung, as well as their usefulness in lung repair and therapy of chronic lung diseases.

Effect of acute lung injury on VLA-4 and CXCR4 expression in resident and circulating hematopoietic stem/progenitor cells.

Background: The effect of acute lung injury on adhesion molecule expression in hematopoietic stem/progenitor cells (HSPCs) is poorly understood.

Objectives: The aim of this study was to determine whether there is a relationship -between pulmonary inflammation, expression of VLA-4 (CD49d), LFA-1 (CD11a), L-selectin (CD62L), CXCR4, and chemotaxis in resident HSPCs, as well as the level of circulating HSPCs.

Methods: Following intratracheal administration of a single LPS bolus in C57Bl/6 mice, the number of inflammatory cells, differential counts, and amounts of cytokines/ chemokines were studied in cytospins and bronchoalveolar lavage fluid (BALF) specimens.

Hematopoietic stem/progenitor cells express functional mitochondrial energy-dependent cystic fibrosis transmembrane conductance regulator.

Bone marrow-derived hematopoietic stem/progenitor cells (HSPCs) encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine. Cystic fibrosis (CF) is one of the diseases whose hope of cure relies on the successful application of cell-based gene therapy.

Stem cell therapy for cystic fibrosis: current status and future prospects.

Although cystic fibrosis (CF), an autosomal recessive disease caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR), seems a good candidate for gene therapy, 15 years of intense investigation and a number of clinical trials have not yet produced a viable clinical gene-therapy strategy. In addition, the duration of gene expression has been shown to be limited, only lasting 1-4 weeks. Therefore, alternative approaches involve the search for, and use of, stem cell populations.

Profibrinolytic activity of the direct thrombin inhibitor melagatran and unfractionated heparin in platelet-poor and platelet-rich clots.

Anticoagulants have been shown to stimulate fibrinolysis principally via inhibition of thrombin-mediated activation of TAFI (thrombin activatable fibrinolysis inhibitor). Their profibrinolytic effect, however, may vary according to their mechanism of action and to the clot composition. We compared the fibrinolytic activity of the direct thrombin inhibitor melagatran with that of unfractionated heparin in platelet-poor (PPP) and platelet-rich (PRP) models consisting of tissue-factor-induced clots exposed to exogenous t-PA (25 ng/ml).

An antifibrinolytic effect associated with an anti-factor V antibody in a patient with severe thrombophilia.

Background And Objectives: The case of a patient with thrombotic manifestations and severe activated protein C resistance due to an anti-factor V antibody has recently been described. Since activated protein C (APC) is also profibrinolytic we wanted to determine whether the presence of antibodies interfering with the anticoagulant activity of APC also inhibits its profibrinolytic effect.

Design And Methods: Plasma clots were formed in the presence of tissue plasminogen activator, thrombin, phospholipids, Ca++, and various concentrations of APC, and the rate of lysis was monitored over time by the reduction in turbidity.

Effect of heparin on TAFI-dependent inhibition of fibrinolysis: relative importance of TAFIa generated by clot-bound and fluid phase thrombin.

Heparin has been proposed to enhance thrombolysis by inhibiting thrombin-dependent generation of activated TAFI (thrombin activatable fibrinolysis inhibitor), a carboxypeptidase that inhibits fibrinolysis. We evaluated the effect of heparin in an in vitro thrombolysis model consisting of a radiolabelled blood clot submerged in defibrinated plasma. Fibrinolysis was induced by adding t-PA (250 ng/ml) and calcium to the plasma bath.