Sequential coronary bifurcation revascularization with the Xposition S™ self-apposing stent: a comparative fractal bench study

International audienc

Characterisation of Mitochondria-associated ER membranes in the enteric nervous system under physiological and pathological conditions

International audienceAlterations in endoplasmic reticulum-mitochondria associations and in mitochondria-associated ER membrane (MAM) behaviour have been reported in the brain in several neurodegenerative diseases. Despite the emerging role of the gut-brain axis in neurodegenerative disorders, the biology of MAM in the enteric nervous system (ENS) has not previously been studied. Therefore, we set out to characterise the MAM in the distal colon of wild type C57BL/6J mice and in senescence accelerated mouse prone 8 (SAMP8), a mouse model of age-related neurodegeneration. We showed for the first time that MAM are widely present in enteric neurons and that their association is altered in SAMP8 mice. We then examined the functions of MAM in a primary culture model of enteric neurons and showed that calcium homeostasis was altered in SAMP8 mice when compared to control animals. These findings provide the first detailed characterisation of MAM in the ENS under physiological conditions and during age-associated neurodegeneration. Further investigation of MAM modifications in the ENS in disease may provide valuable information about the possible role of enteric MAM in neurodegenerative diseases

3D bifurcations characterization for intra-cranial aneurysms prediction

International audienceAn aneurysm is a vascular disorder represented by a ballooning of a blood vessel. The blood vessel's wall is distorted by the blood flow, and a bulge forms there. When ruptured, the aneurysm may cause irreversible damage and could even lead to premature death. Intra-cranial aneurysms are the ones presenting the higher risks. In this work, thanks to a graph based approach, we detect the bifurcations located on the circle of Willis within brain mice cerebral vasculature. Once properly located in the 3D stack, we characterize the cerebral arteries bifurcations, i.e. we gather several properties of the bifurcation, such as their angles, or area cross section, in order to further estimate geometrical patterns that can favor the risk of occurrence of an intra-cranial aneurysm. Effectively, apart from genetic predisposition, and environmental risk factors (high blood pressure, smoking habits, ...) the anatomical disposition of the brain vasculature may influence the chances of an aneurysm to form. Our objectives in this paper is to obtain accurate measurements on the 3D bifurcations

Role of PiT2 in Bone and Adipose Tissues Inter-Communication ?

International audienc

Pullulan microbeads/Si-HPMC hydrogel injectable system for the sustained delivery of GDF-5 and TGF-β1: new insight into intervertebral disc regenerative medicine

Discogenic low back pain is considered a major health concern and no etiological treatments are today available to tackle this disease. To clinically address this issue at early stages, there is a rising interest in the stimulation of local cells by in situ injection of growth factors targeting intervertebral disc (IVD) degenerative process. Despite encouraging safety and tolerability results in clinic, growth factors efficacy may be further improved. To this end, the use of a delivery system allowing a sustained release, while protecting growth factors from degradation appears of particular interest. We propose herein the design of a new injectable biphasic system, based on the association of pullulan microbeads (PMBs) into a cellulose-based hydrogel (Si-HPMC), for the TGF-β1 and GDF-5 growth factors sustained delivery. We present for the first time the design and mechanical characterization of both the PMBs and the called biphasic system (PMBs/Si-HPMC). Their loading and release capacities were also studied and we were able to demonstrate a sustained release of both growth factors, for up to 28 days. Noteworthy, the growth factors biological activity on human cells was maintained. Altogether, these data suggest that this PMBs/Si-HPMC biphasic system may be a promising candidate for the development of an innovative bioactive delivery system for IVD regenerative medicine

Role of PiT2 in Bone and Adipose Tissues Inter-Communication ?

International audienc

PiT1/Slc20a1 is required for endoplasmic reticulum homeostasis, chondrocyte survival and skeletal development: PiT1 regulates ER stress in chondrocytes

International audienceDuring skeletal mineralization, the sodium-phosphate co-transporter PiT1Slc20a1 is assumed to meet the phosphate requirements of bone-forming cells, although evidence is missing. Here, we used a conditional gene deletion approach to determine the role of PiT1 in growth plate chondrocytes. We show that PiT1 ablation shortly after birth generates a rapid and massive cell death in the center of the growth plate, together with an uncompensated ER stress, characterized by morphological changes and increased Chop, Atf4 and Bip expression. PiT1 expression in chondrocytes was not found at the cell membrane but co-localized with the ER marker ERp46, and was up-regulated by the unfolded protein response cascade. In addition, we identified the protein disulfide isomerase (Pdi) ER chaperone as a PiT1 binding partner and showed that PiT1 ablation impaired Pdi reductase activity. The ER stress induced by PiT1 deficiency in chondrocytes was associated with intracellular retention of aggrecan and Vegf-A, which was rescued by over-expressing a phosphate transport-deficient mutant of PiT1. Our data thus reveal a novel, Pi-transport independent function of PiT1, as a critical modulator of ER homeostasis and chondrocyte survival during endochondral ossification. This article is protected by copyright. All rights reserved

Tailored Three-Dimensionally Printed Triply Periodic Calcium Phosphate Implants: A Preclinical Study for Craniofacial Bone Repair

International audienc

Impairing Temozolomide Resistance Driven by Glioma Stem-like Cells with adjuvant Immunotherapy Targeting O-acetyl GD2 Ganglioside: A novel synergistic option for glioblastoma therapy

JF and MB contributed equally to this work.International audienceStem cell chemo-resistance is still challenging the efficacy of the front-line temozolomide against glioblastoma. Novel therapies are urgently needed to fight those cells in order to control tumor relapse. Here, we report that anti-O-acetyl-GD2 adjuvant immunotherapy controls glioma stem-like cell-driven chemo-resistance. Using patient-derived glioblastoma cells we found that glioma stem-like cells over-expressed O-acetyl-GD2. As a result, monoclonal antibody 8B6 immunotherapy significantly increased temozolomide genotoxicity and tumor cell death in vitro by enhancing temozolomide tumor uptake. Furthermore, the combination therapy decreased the expression of the glioma stem-like cell markers CD133 and Nestin and compromised glioma stem-like cell self-renewal capabilities. When tested in vivo, adjuvant 8B6 immunotherapy prevented the extension of the temozolomide-resistant glioma stem-like cell pool within the tumor bulk in vivo and was more effective than the single agent therapies. This is the first report demonstrating that anti-O-acetyl-GD2 monoclonal antibody 8B6 targets glioblastoma in a manner that control temozolomide-resistance driven by glioma stem-like cells. Together our results offer a proof of concept for using anti-O-acetyl GD2 reagents in glioblastoma to develop more efficient combination therapies for malignant gliomas. This article is protected by copyright. All rights reserved

In Situ Forming, Silanized Hyaluronic Acid Hydrogels with Fine Control Over Mechanical Properties and In Vivo Degradation for Tissue Engineering Applications

International audienceIn situ forming hydrogels that can be injected into tissues in a minimally-invasive fashion are appealing as delivery vehicles for tissue engineering applications. Ideally, these hydrogels should have mechanical properties matching those of the host tissue, and a rate of degradation adapted for neo-tissue formation. Here, the development of in situ forming hyaluronic acid hydrogels based on the pH-triggered condensation of silicon alkoxide precursors into siloxanes is reported. Upon solubilization and pH adjustment, the low-viscosity precursor solutions are easily injectable through fine-gauge needles prior to in situ gelation. Tunable mechanical properties (stiffness from 1 to 40 kPa) and associated tunable degradability (from 4 days to more than 3 weeks in vivo) are obtained by varying the degree of silanization (from 4.3% to 57.7%) and molecular weight (120 and 267 kDa) of the hyaluronic acid component. Following cell encapsulation, high cell viability (> 80%) is obtained for at least 7 days. Finally, the in vivo biocompatibility of silanized hyaluronic acid gels is verified in a subcutaneous mouse model and a relationship between the inflammatory response and the crosslink density is observed. Silanized hyaluronic acid hydrogels constitute a tunable hydrogel platform for material-assisted cell therapies and tissue engineering applications