Hyaluronic acid from bluefin tuna by-product: Structural analysis and pharmacological activities.

The fishing and aquaculture industries generate a huge amount of waste during processing and preservation operations, especially those of tuna. Recovering these by-products is a major economic and environmental challenge for manufacturers seeking to produce new active biomolecules of interest. A new hyaluronic acid was extracted from bluefin tuna's vitreous humour to assess its antioxidant and pharmacological activities.

FVIII regulates the molecular profile of endothelial cells: functional impact on the blood barrier and macrophage behavior.

Hemophilia A is an inherited X-linked recessive bleeding disorder caused by deficient activity of blood coagulation factor VIII (FVIII). In addition, hemophilia patients show associated diseases including osteopenia, altered inflammation and vascular fragility which may represent the consequence of recurrent bleeding or may be related to the direct FVIII deficiency. Nowadays, recombinant FVIII is proposed to treat hemophilia patients with no circulating FVIII inhibitor.

Targeting endothelial thioredoxin-interacting protein (TXNIP) protects from metabolic disorder-related impairment of vascular function and post-ischemic revascularisation.

Introduction: Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biological functions, the contribution of endothelial TXNIP has not been well-defined in regards to endothelial and vascular function or in post-ischemic revascularisation. We postulated that inhibition of endothelial TXNIP with siRNA or in a Cre-LoxP system could be involved in protection from high fat, high protein, low carbohydrate (HFHPLC) diet-induced oxidative stress and endothelial dysfunction, leading to vascular damage and impaired revascularisation in vivo.

Methods And Results: To investigate the role of endothelial TXNIP, the TXNIP gene was deleted in endothelial cells using anti-TXNIP siRNA treatment or the Cre-LoxP system.

Ceramide 1-Phosphate Protects Endothelial Colony-Forming Cells From Apoptosis and Increases Vasculogenesis In Vitro and In Vivo.

Objective: Ceramide 1-phosphate (C1P) is a bioactive sphingolipid highly augmented in damaged tissues. Because of its abilities to stimulate migration of murine bone marrow-derived progenitor cells, it has been suggested that C1P might be involved in tissue regeneration. In the present study, we aimed to investigate whether C1P regulates survival and angiogenic activity of human progenitor cells with great therapeutic potential in regenerative medicine such as endothelial colony-orming cells (ECFCs).

In vivo efficacy of endothelial growth medium stimulated mesenchymal stem cells derived from patients with critical limb ischemia.

Background: Cell therapy has been proposed for patients with critical limb ischemia (CLI). Autologous bone marrow derived cells (BMCs) have been mostly used, mesenchymal stem cells (MSCs) being an alternative. The aim of this study was to characterize two types of MSCs and evaluate their efficacy.

and evaluation of a dextran-graft-polybutylmethacrylate copolymer coated on CoCr metallic stent.

The major complications of stent implantation are restenosis and late stent thrombosis. PBMA polymers are used for stent coating because of their mechanical properties. We previously synthesized and characterized Dextrangraft-polybutylmethacrylate copolymer (Dex-PBMA) as a potential stent coating.

Downregulation of Microparticle Release and Pro-Inflammatory Properties of Activated Human Polymorphonuclear Neutrophils by LMW Fucoidan.

Exposition of neutrophils (polymorphonuclear neutrophils, PMNs) to bacterial products triggers exacerbated activation of these cells, increasing their harmful effects on host tissues. We evaluated the possibility of interfering with the classic immune innate responses of human PMNs exposed to bacterial endotoxin (lipopolysaccharide, LPS), and further stimulated with bacterial formyl peptide (N-formyl-methionine-leucine-phenylalanine, fMLP). We showed that the low- molecular-weight fucoidan (LMW-Fuc), a polysaccharide extracted from brown algae, attenuated the exacerbated activation induced by fMLP on LPS-primed PMNs, in vitro, impairing chemotaxis, NET formation, and the pro-survival and pro-oxidative effects.

Osteoprotegerin Induces CD34 Differentiation in Endothelial Progenitor Cells.

Endothelial progenitor cells (EPCs) are the main hypothetical cells that could give rise to vessels and in particular one subtype isolated from peripheral or cord bloods: endothelial colony forming cells (ECFCs). These ECFCs are clonogenic precursors committed to endothelial lineage and have robust vasculogenic properties. However, their low number and poor expansion properties when isolated from human adult bloods, currently limit their use as an autologous cell therapy product.

Arterial Stiffening with Ultrafast Ultrasound Imaging Gives New Insight into Arterial Phenotype of Vascular Ehlers-Danlos Mouse Models.

Objective:  Vascular Ehlers-Danlos syndrome (vEDS) is associated with arterial ruptures due to a mutant gene encoding collagen type III (Col-III). To better understand the role of Col-III, we aimed at evaluating aortic stiffness and dynamic stiffening in vEDS mouse models, with either a quantitative (col3KO mice) or a qualitative Col-III defect (col3KI mice).

Materials And Methods:  Abdominal aortic wall pulse wave velocities (PWV) in col3KO and col3KI mice were compared to their respective wild type (WT) littermates using a 15 MHz ultrafast ultrasonic transducer.

Acidic preconditioning of endothelial colony-forming cells (ECFC) promote vasculogenesis under proinflammatory and high glucose conditions in vitro and in vivo.

Background: We have previously demonstrated that acidic preconditioning of human endothelial colony-forming cells (ECFC) increased proliferation, migration, and tubulogenesis in vitro, and increased their regenerative potential in a murine model of hind limb ischemia without baseline disease. We now analyze whether this strategy is also effective under adverse conditions for vasculogenesis, such as the presence of ischemia-related toxic molecules or diabetes, one of the main target diseases for cell therapy due to their well-known healing impairments.

Methods: Cord blood-derived CD34 cells were seeded in endothelial growth culture medium (EGM2) and ECFC colonies were obtained after 14-21 days.

Nanohybrids with Magnetic and Persistent Luminescence Properties for Cell Labeling, Tracking, In Vivo Real-Time Imaging, and Magnetic Vectorization.

Once injected into a living organism, cells diffuse or migrate around the initial injection point and become impossible to be visualized and tracked in vivo. The present work concerns the development of a new technique for therapeutic cell labeling and subsequent in vivo visualization and magnetic retention. It is hypothesized and subsequently demonstrated that nanohybrids made of persistent luminescence nanoparticles and ultrasmall superparamagnetic iron oxide nanoparticles incorporated into a silica matrix can be used as an effective nanoplatform to label therapeutic cells in a nontoxic way in order to dynamically track them in real-time in vitro and in living mice.

Pulsed cavitational therapy using high-frequency ultrasound for the treatment of deep vein thrombosis in an in vitro model of human blood clot.

Post-thrombotic syndrome, a frequent complication of deep venous thrombosis, can be reduced with early vein recanalization. Pulsed cavitational therapy (PCT) using ultrasound is a recent non-invasive approach. We propose to test the efficacy and safety of high-frequency focused PCT for drug-free thrombolysis (thrombotripsy) in a realistic in vitro model of venous thrombosis.

Osteoprotegerin regulates cancer cell migration through SDF-1/CXCR4 axis and promotes tumour development by increasing neovascularization.

We previously reported that OPG is involved in ischemic tissue neovascularization through the secretion of SDF-1 by pretreated-OPG endothelial colony-forming cells (ECFCs). As the vascularization is one of the key factor influencing the tumour growth and cancer cell dissemination, we investigated whether OPG was able to modulate the invasion of human MNNG-HOS osteosarcoma and DU145 prostate cancer cell lines in vitro and in vivo. Cell motility was analysed in vitro by using Boyden chambers.

Type 2 diabetes alters mesenchymal stem cell secretome composition and angiogenic properties.

This study aimed at characterizing the impact of type 2 diabetes mellitus (T2DM) on the bone marrow mesenchymal stem cell (BMMSC) secretome and angiogenic properties. BMMSCs from Zucker diabetic fatty rats (ZDF) (a T2DM model) and Zucker LEAN littermates (control) were cultured. The supernatant conditioned media (CM) from BMMSCs of diabetic and control rats were collected and analysed.

[Resistance to anti-angiogenic therapy: a clinical and scientific current issue].

Although the use of anti-angiogenic agents has been considered a promising strategy to block tumor growth and improve the bioavailability of drugs into the tumor, the use of most of them in clinical trials is limited. The development of resistance to some anti-angiogenic agents and their high toxicity are currently under investigations. However, the approach is still valid since this therapeutic tool has lengthened survival of patients with colon, breast, kidney, lungs and liver cancers.

Fucoidan Stimulates Monocyte Migration via ERK/p38 Signaling Pathways and MMP9 Secretion.

Critical limb ischemia (CLI) induces the secretion of paracrine signals, leading to monocyte recruitment and thereby contributing to the initiation of angiogenesis and tissue healing. We have previously demonstrated that fucoidan, an antithrombotic polysaccharide, promotes the formation of new blood vessels in a mouse model of hindlimb ischemia. We examined the effect of fucoidan on the capacity of peripheral blood monocytes to adhere and migrate.

Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions.

Unlabelled: : Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.

Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment.

Interleukin-34 (IL-34) was recently characterized as the M-CSF "twin" cytokine, regulating the proliferation/differentiation/survival of myeloid cells. The implication of M-CSF in oncology was initially suspected by the reduced metastatic dissemination in knock-out mice, due to angiogenesis impairment. Based on this observation, our work studied the involvement of IL-34 in the pathogenesis of osteosarcoma.

Acidic preconditioning improves the proangiogenic responses of endothelial colony forming cells.

Objective: Acidosis is present in several pathological conditions where vasculogenesis takes place including ischemia, tumor growth and wound healing. We have previously demonstrated that acidosis induces human CD34+ cell apoptosis. Considering that endothelial colony-forming cells (ECFC) are a subpopulation of CD34+ cells and key players in vasculogenesis, in the present study we investigated the effect of acidosis on the survival and functionality of ECFC.

Targeting VEGFR1 on endothelial progenitors modulates their differentiation potential.

Objectives: We studied whether plasma levels of angiogenic factors VEGF and placental growth factor (PlGF) in coronary artery disease patients or undergoing cardiac surgery are modified, and whether those factors modulate endothelial progenitor's angiogenic potential.

Methods And Results: A total of 143 patients' plasmas from two different studies were analyzed (30 coronary artery disease patients, 30 patients with stable angina, coupled with 30 age and sex-matched controls; 53 patients underwent cardiac surgery). Among factors screened, only PlGF was found significantly increased in these pathological populations.

Mechanistic study of the proangiogenic effect of osteoprotegerin.

Osteoprotegerin (OPG), a soluble tumour necrosis factor receptor superfamily member, inhibits RANKL-mediated osteoclastogenesis. We have previously reported that OPG enhances the proangiogenic properties of endothelial colony-forming cells (ECFCs) in vitro, and promotes vasculogenesis in vivo. Here we investigated how OPG promotes neovascularisation.

A motif within the N-terminal domain of TSP-1 specifically promotes the proangiogenic activity of endothelial colony-forming cells.

Thrombospondin-1 (TSP-1) gives rise to fragments that have both pro- and anti-angiogenic effects in vitro and in vivo. The TSP-HepI peptide (2.3 kDa), located in the N-terminal domain of TSP-1, has proangiogenic effects on endothelial cells.

Therapeutic effect of fucoidan-stimulated endothelial colony-forming cells in peripheral ischemia.

Background: Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro.

Objectives: We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo.

Methods: We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair.

Osteoprotegerin, a new actor in vasculogenesis, stimulates endothelial colony-forming cells properties.

Background: Osteoprotegerin (OPG), a soluble receptor of the tumour necrosis factor family, and its ligand, the receptor activator of nuclear factor-κB ligand (RANKL), are emerging as important regulators of vascular pathophysiology.

Objectives: We evaluated their effects on vasculogenesis induced by endothelial colony-forming cells (ECFC) and on neovessel formation in vivo.

Methods: Effects of OPG and RANKL on in vitro angiogenesis were evaluated after ECFC incubation with OPG or RANKL (0-50 ng mL(-1)).

Thrombospondin-1 is a plasmatic marker of peripheral arterial disease that modulates endothelial progenitor cell angiogenic properties.

Objective: We examined whether plasma levels of angiogenic factors are altered in plasma of patients with peripheral arterial disease (PAD) and whether these factors affect endothelial progenitor cell-induced angiogenesis.

Methods And Results: Plasma was collected from 184 patients with PAD and 330 age-matched healthy controls. Vascular endothelial growth factor and placental growth factor concentrations did not differ between the groups, whereas we found a linear correlation between PAD disease and thrombospondin (TSP)-1 plasma level.