Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation

in Transplantation (2013), 95(3), 426-433

Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ... [more ▼]

Background: Cryopreservation of cortex ovarian tissue before anti-cancer therapy is a promising technique for fertility preservation mainly in children and young women. Ischemia in the early stage after ovarian graft causes massive follicle loss by apoptosis. VEGF111 is a recently described VEGF isoform that does not bind to the extracellular matrix, diffuse extensively and is resistant to proteolysis. These properties confer a significantly higher angiogenic potential to VEGF111 in comparison to the other VEGF isoforms. Methods: We evaluated the morphology of cryopreserved sheep ovarian cortex, grafted in the presence or absence of VEGF111. Ovarian cortex biopsies were embedded in type I collagen with or without VEGF111 addition before transplantation to SCID mice ovaries. Transplants were retrieved 3 days or 3 weeks later. Follicular density, vasculature network, haemoglobin content and cell proliferation were analysed. Results: Addition of VEGF111 increased density of functional capillaries (p=0.01) 3 days after grafting. By double immunostaining of Ki-67 and von Willebrand Factor (vWF) we demonstrated that proliferating endothelial cells were found in 83% of the VEGF111 group when compared to 33% in the control group (p=0.001). This angio-stimulation was associated with a significant enhancement of haemoglobin content (p=0.03). Three weeks after transplantation, the number of primary follicles was significantly higher in VEGF111 grafts (p=0.02). Conclusion: VEGF111 accelerates blood vessels recruitment, functional angiogenesis and improves the viability of ovarian cortex by limiting ischemia and ovarian cortex damage. [less ▲]

Influence of type of contraction upon tendinous tissue during training: animal model

in Meeusen, R; Duchateau, J; Roelands, B (Eds.) et al Book of Abstracts of the 17th annual Congress of the ECSS (2012, July)

Introduction: The treatment of choice for tendinopathies is eccentric reeducation. Although the clinical results appear favourable, the biomechanical changes to the tissue are not yet clear. Materiel and ... [more ▼]

Introduction: The treatment of choice for tendinopathies is eccentric reeducation. Although the clinical results appear favourable, the biomechanical changes to the tissue are not yet clear. Materiel and methods: This study compared the effects of two methods of training (eccentric (E) training and concentric (C) training) with untrained (U) rats. The animals underwent training over a period of five weeks. The tricipital, patellar and Achilles tendons were subsequently removed to perform a traction test to the point of tendon rupture, and a histological analysis was performed. Results: There was a significant improvement in the rupture force of the patellar and tricipital tendons between the U and E groups. The tricipital tendons in the control group presented a significantly smaller cross-section than the E- and C-trained groups. No significant difference was observed for the constraints between the three groups for all three tendons. However, a tendency towards improvement was observed between the trained and the U groups for the patellar tendon. Histological studies demonstrated the development of a greater number of blood vessels and a larger quantity of collagen in the eccentric group. Discussion and conclusion: The mechanical properties of tendons in rats improve after specific training, especially following eccentric training. [less ▲]

The angiogenesis suppressor gene AKAP12 is under the epigenetic control of HDAC7 in endothelial cells.

Conference (2012, April 21)

Metallothionein-dependent up-regulation of TGF-B2 participates in the remodelling of the myxomatous mitral valve.

in Cardiovascular Research (2012), 93(3), 480-9

Isoform 111 of vascular endothelial growth factor (VEGF111) improves angiogenesis of ovarian tissue xenotransplantation

in Journal of Assisted Reproduction & Genetics (2012), 28(11), 1009

New prospects in the roles of the C-terminal domains of VEGF-A and their cooperation for ligand binding, cellular signaling and vessels formation.

in Angiogenesis (2012), sous presse

VEGF-A is a crucial growth factor for blood vessel homeostasis and pathological angiogenesis. Due to alternative splicing of its pre-mRNA, VEGF-A is produced under several isoforms characterized by the ... [more ▼]

VEGF-A is a crucial growth factor for blood vessel homeostasis and pathological angiogenesis. Due to alternative splicing of its pre-mRNA, VEGF-A is produced under several isoforms characterized by the combination of their C-terminal domains, which determines their respective structure, availability and affinity for co-receptors. As controversies still exist about the specific roles of these exon-encoded domains, we systematically compared the properties of eight natural and artificial variants containing the domains encoded by exons 1-4 and various combinations of the domains encoded by exons 5, 7 and 8a or 8b. All the variants (VEGF(111)a, VEGF(111)b, VEGF(121)a, VEGF(121)b, VEGF(155)a, VEGF(155)b, VEGF(165)a, VEGF(165)b) have a similar affinity for VEGF-R2, as determined by Surface plasmon resonance analyses. They strongly differ however in terms of binding to neuropilin-1 and heparin/heparan sulfate proteoglycans. Data indicate that the 6 amino acids encoded by exon 8a must be present and cooperate with those of exons 5 or 7 for efficient binding, which was confirmed in cell culture models. We further showed that VEGF(165)b has inhibitory effects in vitro, as previously reported, but that the shortest VEGF variant possessing also the 6 amino acids encoded by exon 8b (VEGF(111)b) is remarkably proangiogenic, demonstrating the critical importance of domain interactions for defining the VEGF properties. The number, size and localization of newly formed blood vessels in a model of tumour angiogenesis strongly depend also on the C-terminal domain composition, suggesting that association of several VEGF isoforms may be more efficient for treating ischemic diseases than the use of any single variant. [less ▲]

The mice drawer system (MDS) tissue sharing programme: effect of space conditions on skin metabolic activity.

Conference (2012)

Chitosan-based biomimetic scaffolds and methods for preparing the same

Patent (2011)

The invention concerns chitosan-based biomimetic scaffolds and methods for modulating their intrinsic properties such as rigidity, elasticity, resistance to mechanical stress, porosity, biodegradation and ... [more ▼]

The invention concerns chitosan-based biomimetic scaffolds and methods for modulating their intrinsic properties such as rigidity, elasticity, resistance to mechanical stress, porosity, biodegradation and absorbance of exudates. Therefore, the present invention relates to a layered chitosan-based scaffold wherein said layered scaffold comprises at least two fused layers, wherein at least one layer consists of a chitosan nanofiber scaffold membrane and at least one of the other layers of a porous chitosan scaffold support layer. Moreover, the present invention provides a layered chitosan-based scaffold characterized by (i) a good adhesion between the porous and nanofiber layers, (ii) a tuneable porosity of the nanofiber layer by tuning the distance between the nanofibers, (iii) a stable nanofibers and porous morphology even when immersed in water or other solvents and a process for the preparation of such layered chitosan-based scaffold.Finally, the present invention provides the use of the layered electrospun chitosan-based scaffold of the invention or the layered electrospun chitosan-based scaffold produced by the process of the invention as a wound dressing, in tissue engineering or for biomedical applications. [less ▲]

Human papillomavirus entry into NK cells requires CD16 expression and triggers cytotoxic activity and cytokine secretion.

in European journal of immunology (2011), 41(11), 3240-3252

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV ... [more ▼]

Human papillomavirus (HPV) infections account for more than 50% of infection-linked cancers in women worldwide. The immune system controls, at least partially, viral infection and around 90% of HPV-infected women clear the virus within two years. However, it remains unclear which immune cells are implicated in this process and no study has evaluated the direct interaction between HPVs and NK cells, a key player in host resistance to viruses and tumors. We demonstrated an NK cell infiltration in HPV-associated pre-neoplastic cervical lesions. Since HPVs cannot grow in vitro, virus-like particles (VLPs) were used as a model for studying the NK cell response against the virus. Interestingly, NK cells displayed higher cytotoxic activity and cytokine production (TNF-alpha and IFN-gamma) in the presence of HPV-VLPs. Using flow cytometry and microscopy we observed that NK cell stimulation was linked to rapid VLP entry into these cells by macropinocytosis. Using CD16(+) and CD16(-) NK cell lines and a CD16-blocking antibody, we demonstrated that CD16 is necessary for HPV-VLP internalization, as well as for degranulation and cytokine production. Thus, we show for the first time that NK cells interact with HPVs and can participate in the immune response against HPV-induced lesions. [less ▲]

Plasma enrichi en plaquettes et cicatrisation tendineuse : modèle sur rats

in Annales de Réadaptation et de Médecine Physique (2011, October), 54(1), 123

Introduction: Le but de notre étude était de déterminer si une injection de plasma enrichi en plaquettes (PRP) pouvait améliorer et accélérer le processus de cicatrisation de tendons d'Achille de rats ... [more ▼]

Introduction: Le but de notre étude était de déterminer si une injection de plasma enrichi en plaquettes (PRP) pouvait améliorer et accélérer le processus de cicatrisation de tendons d'Achille de rats rompus. Matériel et méthode : Un défect de 5mm a été réalisé chirurgicalement au niveau de tendons d'Achille de 120 rats. Soixante rats ont reçu respectivement une infiltration de PRP ou PBS in situ après chirurgie. Vingt rats de chaque groupe ont été euthanasiés après 5, 15 et 30 jours. Quinze tendons de chaque groupe ont été directement soumis à un test de traction biomécanique jusqu'à rupture à l'aide de clamps de type "cryo-jaw" et ensuite collectés pour réaliser des analyses transcriptomiques. Des études histologique et biochimique ont également été réalisées sur les 5 tendons restant de chaque groupe. Résultats: Les tendons du groupe PRP étaient plus résistants à la rupture à 15 et 30 jours que ceux du groupe contrôle. La section transverse des tendons était significativement plus grande au sein du groupe PRP à J5 et J15. Les contraintes étaient significativement plus grandes au sein des tendons dans les phases tardives de cicatrisation. L'étude histologique montrait une augmentation de coloration pour les fibres de collagène à J5 au sein du groupe PRP, résultats confirmés par l'analyse biochimique montrant une augmentation de la concentration de collagène au sein du "cal" tendineux. L'expression de la ténomoduline, un marqueur de la différentiation des ténocytes, était significativement plus important au sein du groupe PRP à J5. Aucune différence significative en terme d'ARNm n'a été observée pou r le collagène de type III ni pour la MMP-9, à aucun temps, entre les 2 groupes. Conclusion : Une injection de PRP au sein de tendons d'Achille de rats rompus influence les phases précoces du la cicatrisation tendineuse, entrainant une meilleure résistance mécanique à la rupture. [less ▲]