The multilayer flow modulator (MFM; Cardiatis, Isnes, Belgium) is a self-expandable mesh of braid... more The multilayer flow modulator (MFM; Cardiatis, Isnes, Belgium) is a self-expandable mesh of braided cobalt alloy wires, used for treatment of aortic and peripheral aneurysms. To further improve our understanding of this novel technology, the endothelialization kinetics of the MFM was investigated and compared with those of two marketed single-layer stents. Five porcine animal models were used in which a total of 19 stents were implanted in the iliac and carotid arteries between one and five weeks before sacrifice. All 19 stents were successfully delivered. For all devices, nonsignificant signs of inflammation or thrombosis were noted, and there was no evidence of local intolerance. The MFM developed a thin layer of endothelial cells earlier and was associated with less neointimal development than the two single-layer stents. A differing phenomenon of integration was also revealed and hypothesized as endothelialization from adhesion of circulating endothelial progenitor cells, as wel...
Dendritic cells (DC) are recognized as sentinels, which capture antigens in tissue and migrate to... more Dendritic cells (DC) are recognized as sentinels, which capture antigens in tissue and migrate to the lymph node, where they initiate immune responses. However, when a vaccine strain of green fluorescent protein-expressing Salmonella abortusovis (SAO) was inoculated into sheep oral mucosa, it induced accumulation of myeloid non-DC in the subcapsular sinus and paracortex of the draining lymph node, and SAO was mainly found associated with these cells (granulocytes and macrophages) but rarely with DC. To analyze how bacteria reached lymph nodes, we used cervical pseudo-afferent lymph duct catheterization. We showed that Salmonella administered in the oral mucosa were traveling free in lymph or associated with cells, largely with lymph monocytes and granulocytes but less with DC. SAO also induced a strong influx of these phagocytic cells in afferent lymph. Migrating DC presented a semi-mature phenotype, and SAO administration did not alter their expression of major histocompatibility c...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 2014
Swine skin is one of the best structural models for human skin, widely used to probe drug transcu... more Swine skin is one of the best structural models for human skin, widely used to probe drug transcutaneous passage and to test new skin vaccination devices. However, little is known about its composition in immune cells, and among them dendritic cells (DC), that are essential in the initiation of the immune response. After a first seminal work describing four different DC subpopulations in pig skin, we hereafter deepen the characterization of these cells, showing the similarities between swine DC subsets and their human counterparts. Using comparative transcriptomic study, classical phenotyping as well as in vivo and in vitro functional studies, we show that swine CD163(pos) dermal DC (DDC) are transcriptomically similar to the human CD14(pos) DDC. CD163(pos) DDC are recruited in inflamed skin, they migrate in inflamed lymph but they are not attracted toward CCL21, and they modestly activate allogeneic CD8 T cells. We also show that CD163(low) DDC are transcriptomically similar to the...
Dendritic cells (DC) in peripheral tissues are considered as immature cells that mature and migra... more Dendritic cells (DC) in peripheral tissues are considered as immature cells that mature and migrate towards lymph nodes upon stimulation with pathogens. This commonly accepted paradigm is challenged by the fact that tolerance to peripheral self antigen is controlled by mature DC and that DC collected from afferent lymph draining different tissues from several species, in the absence of pathogen signaling, were inconsistently found to be either at a mature or semi-mature state. In order to better define the maturation state of DC that migrate in lymph in absence of pathogen stimulation, we compared skin lymph DC to resident and LPS (lipopolysaccharide)-activated skin DC thanks to the establishment of a mini-pig model of lymph duct cannulation. Based on their co-stimulatory molecules expression and endocytotic capacities, pig lymph skin DC were found at an intermediate state of maturation between resident and LPS-activated skin DC and were fully capable of allogeneic T cell stimulation. Furthermore, lymph skin DC could be further matured by LPS or influenza stimulation. Thus, using the pig skin model which is relevant to human, we show that skin-derived DC constantly migrate at an intermediate state of maturation that can be further enhanced upon appropriate stimulation.
Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as ... more Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC) and dermal DC (DDC) that could be divided in 3 subsets according to their phenotypes: (1) the CD163 neg /CD172a neg , (2) the CD163 high CD172a pos and (3) the CD163 low CD172a pos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163 high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163 neg CD172 low DDC share properties with the CD8 + T cell response-inducing murine skin CD103 pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.
This study tested the hypothesis that the Multilayer Flow Modulator (Cardiatis, Isnes, Brussels) ... more This study tested the hypothesis that the Multilayer Flow Modulator (Cardiatis, Isnes, Brussels) can treat aortic aneurysms through intra-arterial hemodynamic modulation, without substantial parent or small branch artery compromise, using 8 porcine models. The animals were euthanized and devices explanted upon completion of the study for examination. Results of the delivery system evaluation showed that there were no difficulties during navigation of the device through the arteries. An overall trend of reduction in aneurysm size was recorded. The opening of the aneurysm was nearly occluded with thrombus in 2 of the explants. The visceral arteries covered by the device remained patent, and it adhered to the arterial wall with endothelialization clearly visible. The MFM was therefore placed without intra-arterial compromise, and the aneurysms were stabilized while adequate blood flow to the collateral arteries was preserved.
The multilayer flow modulator (MFM; Cardiatis, Isnes, Belgium) is a self-expandable mesh of braid... more The multilayer flow modulator (MFM; Cardiatis, Isnes, Belgium) is a self-expandable mesh of braided cobalt alloy wires, used for treatment of aortic and peripheral aneurysms. To further improve our understanding of this novel technology, the endothelialization kinetics of the MFM was investigated and compared with those of two marketed single-layer stents. Five porcine animal models were used in which a total of 19 stents were implanted in the iliac and carotid arteries between one and five weeks before sacrifice. All 19 stents were successfully delivered. For all devices, nonsignificant signs of inflammation or thrombosis were noted, and there was no evidence of local intolerance. The MFM developed a thin layer of endothelial cells earlier and was associated with less neointimal development than the two single-layer stents. A differing phenomenon of integration was also revealed and hypothesized as endothelialization from adhesion of circulating endothelial progenitor cells, as wel...
Dendritic cells (DC) are recognized as sentinels, which capture antigens in tissue and migrate to... more Dendritic cells (DC) are recognized as sentinels, which capture antigens in tissue and migrate to the lymph node, where they initiate immune responses. However, when a vaccine strain of green fluorescent protein-expressing Salmonella abortusovis (SAO) was inoculated into sheep oral mucosa, it induced accumulation of myeloid non-DC in the subcapsular sinus and paracortex of the draining lymph node, and SAO was mainly found associated with these cells (granulocytes and macrophages) but rarely with DC. To analyze how bacteria reached lymph nodes, we used cervical pseudo-afferent lymph duct catheterization. We showed that Salmonella administered in the oral mucosa were traveling free in lymph or associated with cells, largely with lymph monocytes and granulocytes but less with DC. SAO also induced a strong influx of these phagocytic cells in afferent lymph. Migrating DC presented a semi-mature phenotype, and SAO administration did not alter their expression of major histocompatibility c...
Journal of immunology (Baltimore, Md. : 1950), Jan 15, 2014
Swine skin is one of the best structural models for human skin, widely used to probe drug transcu... more Swine skin is one of the best structural models for human skin, widely used to probe drug transcutaneous passage and to test new skin vaccination devices. However, little is known about its composition in immune cells, and among them dendritic cells (DC), that are essential in the initiation of the immune response. After a first seminal work describing four different DC subpopulations in pig skin, we hereafter deepen the characterization of these cells, showing the similarities between swine DC subsets and their human counterparts. Using comparative transcriptomic study, classical phenotyping as well as in vivo and in vitro functional studies, we show that swine CD163(pos) dermal DC (DDC) are transcriptomically similar to the human CD14(pos) DDC. CD163(pos) DDC are recruited in inflamed skin, they migrate in inflamed lymph but they are not attracted toward CCL21, and they modestly activate allogeneic CD8 T cells. We also show that CD163(low) DDC are transcriptomically similar to the...
Dendritic cells (DC) in peripheral tissues are considered as immature cells that mature and migra... more Dendritic cells (DC) in peripheral tissues are considered as immature cells that mature and migrate towards lymph nodes upon stimulation with pathogens. This commonly accepted paradigm is challenged by the fact that tolerance to peripheral self antigen is controlled by mature DC and that DC collected from afferent lymph draining different tissues from several species, in the absence of pathogen signaling, were inconsistently found to be either at a mature or semi-mature state. In order to better define the maturation state of DC that migrate in lymph in absence of pathogen stimulation, we compared skin lymph DC to resident and LPS (lipopolysaccharide)-activated skin DC thanks to the establishment of a mini-pig model of lymph duct cannulation. Based on their co-stimulatory molecules expression and endocytotic capacities, pig lymph skin DC were found at an intermediate state of maturation between resident and LPS-activated skin DC and were fully capable of allogeneic T cell stimulation. Furthermore, lymph skin DC could be further matured by LPS or influenza stimulation. Thus, using the pig skin model which is relevant to human, we show that skin-derived DC constantly migrate at an intermediate state of maturation that can be further enhanced upon appropriate stimulation.
Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as ... more Transcutaneous delivery of vaccines to specific skin dendritic cells (DC) subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC) and dermal DC (DDC) that could be divided in 3 subsets according to their phenotypes: (1) the CD163 neg /CD172a neg , (2) the CD163 high CD172a pos and (3) the CD163 low CD172a pos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163 high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163 neg CD172 low DDC share properties with the CD8 + T cell response-inducing murine skin CD103 pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.
This study tested the hypothesis that the Multilayer Flow Modulator (Cardiatis, Isnes, Brussels) ... more This study tested the hypothesis that the Multilayer Flow Modulator (Cardiatis, Isnes, Brussels) can treat aortic aneurysms through intra-arterial hemodynamic modulation, without substantial parent or small branch artery compromise, using 8 porcine models. The animals were euthanized and devices explanted upon completion of the study for examination. Results of the delivery system evaluation showed that there were no difficulties during navigation of the device through the arteries. An overall trend of reduction in aneurysm size was recorded. The opening of the aneurysm was nearly occluded with thrombus in 2 of the explants. The visceral arteries covered by the device remained patent, and it adhered to the arterial wall with endothelialization clearly visible. The MFM was therefore placed without intra-arterial compromise, and the aneurysms were stabilized while adequate blood flow to the collateral arteries was preserved.
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Papers by Michel Bonneau