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See detailComprehensive analysis of the immunomodulatory effects of rapamycin on human T cells in graft-versus-host disease prophylaxis
Ehx, Grégory ULiege; Ritacco, Caroline ULiege; HANNON, Muriel ULiege et al

in American Journal of Transplantation (in press)

Graft-versus-host disease (GVHD) is a major cause of toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). While rapamycin (RAPA) is commonly used in GVHD prophylaxis in combination ... [more ▼]

Graft-versus-host disease (GVHD) is a major cause of toxicity after allogeneic hematopoietic cell transplantation (allo-HCT). While rapamycin (RAPA) is commonly used in GVHD prophylaxis in combination with a calcineurin inhibitor (CNI), the understanding of its mechanism of action on human T cells is still incomplete. Here, we performed an extensive analysis of RAPA effects on human T cells in a humanized mouse model of GVHD, in ex-vivo T-cell cultures and in patients given RAPA plus tacrolimus as GVHD prophylaxis after non-myeloablative allo-HCT. We demonstrate that RAPA mitigates GVHD by decreasing T-cell engraftment and differentiation, inhibiting CD8+ T-cell activation and increasing the long-term IL-2 secretion, thereby supporting regulatory T-cell (Treg) proliferation. In contrast, graft-versus-leukemia effects were not abrogated, as RAPA-treated T cells had increased resistance to apoptosis and retained their effector function and proliferative capacity upon re-stimulation. Importantly, we found that RAPA impact on Treg and CD8+ T cells was closely dependent upon IL-2 signaling and that therapeutic options interfering with IL-2, such as calcineurin inhibitors, antagonize the IL-2-dependent promotion of Treg mediated by RAPA. Our results suggest that RAPA immunological efficacy could be improved in combination with drugs having possible synergistic effects such as the hypomethylating agent 5-azacytidine. [less ▲]

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See detail"Opter pour l'obligation vaccinale est un choix de société"
Muraille, Eric; De Kerchove d'Exaerde, Alban; Drion, Pierre ULiege et al

Article for general public (2021)

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See detailLocal anisotropy in mineralized fibrocartilage and subchondral bone beneath the tendon-bone interface
Tits, Alexandra ULiege; Plougonven, Erwan ULiege; Blouin, Stéphane et al

in Scientific Reports (2021), 11

The enthesis allows the insertion of tendon into bone thanks to several remarkable strategies. This complex and clinically relevant location often features a thin layer of fibrocartilage sandwiched ... [more ▼]

The enthesis allows the insertion of tendon into bone thanks to several remarkable strategies. This complex and clinically relevant location often features a thin layer of fibrocartilage sandwiched between tendon and bone to cope with a highly heterogeneous mechanical environment. The main purpose of this study was to investigate whether mineralized fibrocartilage and bone close to the enthesis show distinctive three-dimensional microstructural features, possibly to enable load transfer from tendon to bone. As a model, the Achilles tendon-calcaneus bone system of adult rats was investigated with histology, backscattered electron imaging and micro-computed tomography. The microstructural porosity of bone and mineralized fibrocartilage in different locations including enthesis fibrocartilage, periosteal fibrocartilage and bone away from the enthesis was characterized. We showed that calcaneus bone presents a dedicated protrusion of low porosity where the tendon inserts. A spatially resolved analysis of the trabecular network suggests that such protrusion may promote force flow from the tendon to the plantar ligament, while partially relieving the trabecular bone from such a task. Focusing on the tuberosity, highly specific microstructural aspects were highlighted. Firstly, the interface between mineralized and unmineralized fibrocartilage showed the highest roughness at the tuberosity, possibly to increase failure resistance of a region carrying large stresses. Secondly, fibrochondrocyte lacunae inside mineralized fibrocartilage, in analogy with osteocyte lacunae in bone, had a predominant alignment at the enthesis and a rather random organization away from it. Finally, the network of subchondral channels inside the tuberosity was highly anisotropic when compared to contiguous regions. This dual anisotropy of subchondral channels and cell lacunae at the insertion may reflect the alignment of the underlying collagen network. Our findings suggest that the microstructure of fibrocartilage may be linked with the loading environment. Future studies should characterize those microstructural aspects in aged and or diseased conditions to elucidate the poorly understood role of bone and fibrocartilage in enthesis-related pathologies. [less ▲]

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See detailMesenchymal stromal cells combined with everolimus promote Treg expansion but do not synergize in a rat liver transplant rejection model
VANDERMEULEN, Morgan ULiege; ERPICUM, Pauline ULiege; BLETARD, Noëlla ULiege et al

in Transplant International (2021, August), 34(S1 OP519), 101

Background: Mesenchymal stromal cells (MSCs) have particular properties that can be of interest in organ transplantation, including expansion of regulatory T cells (Tregs), a key factor in graft tolerance ... [more ▼]

Background: Mesenchymal stromal cells (MSCs) have particular properties that can be of interest in organ transplantation, including expansion of regulatory T cells (Tregs), a key factor in graft tolerance induction. The immunosuppression to be associated with MSCs has not yet been defined. Additionally, the impact of the association of everolimus with MSCs on Treg expansion and on induction of liver graft tolerance has never been studied. The aim of this study was to evaluate the effects of MSCs combined, or not, with everolimus, on Treg expansion and in a model of liver transplantation (LT) rejection in the rat. Methods: Firstly, Lewis rats received intravenous MSCs at D9 with/without subcutaneous everolimus from D0 to D14. Analysis of circulating Tregs was performed at D0, D14 and D28. Secondly, 48 h after LT with a Dark Agouti rat liver, 30 Lewis rats were randomized in 3 groups: everolimus (subcutaneous for 14 days), MSCs (intravenous injection at D2 and D9), or both everolimus and MSCs. Rejection of the liver graft was assessed by liver tests, histology and survival. Results: Individually, MSC infusion and everolimus promoted Treg expansion in rats, and everolimus had no negative impact on Treg expansion when combined with MSCs. However, in the LT model, injections of MSCs 2 and 9 days following LT were not effective at preventing acute rejection, and the combination of MSCs with everolimus failed to show any synergistic effect when compared to everolimus alone. Conclusion: Everolimus may be used in association with MSCs. However, in our model of LT in the rat, post-transplant MSC injections did not prevent acute rejection, and the association of MSCs with everolimus did not show any synergistic effect. [less ▲]

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See detailCrise Covid: pourrait-on breveter le soleil? (carte blanche)
Drion, Pierre ULiege; Cloots, Rudi ULiege

Article for general public (2021)

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See detailLocal adaptation of bone micro-structure and canal network to tendon insertion investigated by image-based micro-FE simulations
Tits, Alexandra ULiege; Varga, Peter; Volders, Timothy ULiege et al

in Bone Reports (2020, October), 13

Tendons anchor to bone through a multi-material region called enthesis, showing several strategies to cope with the challenging task of joining dissimilar tissues. Less understood is whether bone ... [more ▼]

Tendons anchor to bone through a multi-material region called enthesis, showing several strategies to cope with the challenging task of joining dissimilar tissues. Less understood is whether bone microstructure also displays specific features to facilitate force transmission from tendon to bone. Such knowledge is of clinical relevance as local mechanical stresses play a crucial role in avulsion fractures and interface pathologies. Here we characterized the microstructure of bone close to tendon insertion in calcanei of adult rats (n=5) with micro-computed tomography (SkyScan, Bruker; 5 to 1.2 micrometer voxel size). After aligning the virtual bones along the main axes of inertia, we investigated a bony tuberosity connecting the Achilles tendon with the plantar fascia ligament. We performed a spatially resolved analysis of trabecular microstructure, indicating that trabecular network (BV/TV and anisotropy) is not significantly influenced by the tendon insertion (P = 0.69). Conversely, high resolution images revealed that bone beneath the attachment region exhibits a highly oriented canal network, aligned with the pulling direction of the tendon (P b 0.005). Image-based micro-finite element analysis was used to calculate stresses within the bone induced by tendon loading. Simulations highlighted a non-trivial stress pattern within the bone with high stresses mainly flowing within the tuberosity (27% higher than in the rest of the bone, P b 0.005). Our work suggests that not only the enthesis but also the underlying bone is well-adapted to accommodate tendon loading. [less ▲]

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See detailPractical considerations for reducing mortality rates in alloxan-induced diabetic rabbits
BACEVIC, Miljana ULiege; Rompen, Eric ULiege; RADERMECKER, Régis ULiege et al

in Heliyon (2020)

Chemically-induced diabetic animal models have been employed in many areas of diabetes mellitus (DM) research, but managing post-induction animal survival rates remains one of the main downsides. The aim ... [more ▼]

Chemically-induced diabetic animal models have been employed in many areas of diabetes mellitus (DM) research, but managing post-induction animal survival rates remains one of the main downsides. The aim of the present study was to propose a reliable approach to animal management and monitoring after DM induction in a rabbit model in order to reduce animal mortality rates. DM was induced by injecting alloxan in 12 New Zealand White rabbits. A preventive subcutaneous glucose administration to counteract a potentially lethal hypoglycemic phase following alloxan injection was performed on individual bases. Blood glucose level (BGL) was checked hourly for the first 36 hours, then every 2 hours until the hyperglycemic state was confirmed. All 12 rabbits survived a 48-hour post-induction phase. The critical hypoglycemic phase’s start points and duration differed significantly among the rabbits, lasting from 6.7 to 37 hours (19.75 ± 8.44). The rabbits entered the final hyperglycemic phase 18 hours at the earliest and 42 hours at the latest after induction (26.63 ± 7.07). The average daily BGLs throughout the study period ranged from 268 to 512 (413.73 ± 76.69). Eleven rabbits survived until the end of the experiment. The variability of rabbits’ responses to alloxan injection emphasizes the importance of monitoring rabbit behavior and thoroughly checking BGLs, followed by a preventive glucose administration based on rabbits’ individual needs for up to 36 hours after alloxan injection. The proposed approach seems to reduce animal mortality. [less ▲]

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See detailPlatelet-rich plasma (PRP) and tendon healing: comparison between fresh and frozen-thawed PRP
KAUX, Jean-François ULiege; Libertiaux, Vincent; Dupont, Laura ULiege et al

in Platelets (2020), 31(2), 221-225

Platelet-rich plasma (PRP) is increasingly used in the treatment of musculoskeletal diseases. Its preservation by freezing it for the realization of multiple injections in clinical use has never been ... [more ▼]

Platelet-rich plasma (PRP) is increasingly used in the treatment of musculoskeletal diseases. Its preservation by freezing it for the realization of multiple injections in clinical use has never been discussed. Calcaneal tendons of rats were surgically sectioned. Platelet concentration of the PRP was 2.5 x 106/μl with autologous plasma of rats. Frozen-thawed PRP was prepared by performing two cycles of freezing and thawing on PRP aliquots. Both platelet preparations were injected in the lesion. Biomechanical and histological evaluations were carried out after 7, 20 or 40 days post surgery. After 7 and 40 days, no significant difference was observed between the PRP and the frozen-thawed PRP group. There is however a difference 20 days after surgery: the ultimate tensile strength (UTS) was greater in the fresh PRP group. No obvious difference with histological aspect was observed between the two groups. In conclusion, fresh PRP and frozen-thawed PRP injections can lead to similar results in the healing process of section calcaneal tendons of rats. Improvements with fresh PRP are slight. PRP could thus be frozen to be preserved if multiple injections are needed (e.g. osteoarthritis). [less ▲]

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See detailMicrostructural and micromechanical investigation of the tendon-bone attachment
Tits, Alexandra ULiege; KAUX, Jean-François ULiege; Plougonven, Erwan ULiege et al

Conference (2019, December 17)

We observed an evident bony tuberosity connecting the Achilles tendon with the plantar fascia ligament. We performed a spatially resolved analysis of trabecular microstructure, suggesting that trabecular ... [more ▼]

We observed an evident bony tuberosity connecting the Achilles tendon with the plantar fascia ligament. We performed a spatially resolved analysis of trabecular microstructure, suggesting that trabecular network was not significantly influenced by the tendon insertion. Conversely, bone beneath the attachment region showed a highly oriented canal network, aligned along the pulling direction of the tendon. Surface roughness was significantly higher at the tendon insertion with respect to nearby locations. Micro-FE simulations clarified the contributions of these different microstructural features to local stresses. [less ▲]

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See detailL’expérimentation animale : toujours une nécessité pour la santé animale et humaine
Balthazart, Jacques ULiege; Blanpain, Cédric; Bureau, Fabrice ULiege et al

Article for general public (2019)

Le 1 juillet 2019, « Le Soir » publiait un article relatant la découverte par les chercheurs de l'UCLouvain d'une bactérie pouvant potentiellement contribuer à limiter les risques cardiovasculaires , l ... [more ▼]

Le 1 juillet 2019, « Le Soir » publiait un article relatant la découverte par les chercheurs de l'UCLouvain d'une bactérie pouvant potentiellement contribuer à limiter les risques cardiovasculaires , l'une des premières causes de décès en Belgique. Cet article soulignait l'importance de la recherche fondamentales et du passage nécessaire par l'expérimentation préclinique (animale) pour développer une application chez l’humain. En réaction, Solange T'Kint, administratrice de l'ASBL S.E.A. - Suppression des Expériences sur l'Animal-, publiait le 2 juillet dans « La Libre » un nouveau pamphlet contre l'expérimentation animale. Mme T Kint avait déjà lancé en aout 2018 une pétition attaquant la découverte3 d'un chercheur de l'ULB sur la dépendance aux drogues réalisée chez la souris , démontrant par là à quel point toute avancée médicale imputable à l'expérimentation animale lui est insupportable. Ici se trouve la réponse de Scientifiques qui pensent indispensable d’informer chacun-e- de manière rigoureuse et de ne jamais laisser diffuser de « fake news » sans réagir. [less ▲]

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See detailStructural and mechanical analysis of calcaneus bone at the Achilles tendon insertion site
Tits, Alexandra ULiege; KAUX, Jean-François ULiege; Fernandez, Justin et al

Conference (2019, July)

We highlighted a morphological protrusion facilitating load transmission from the Achilles tendon to the plantar ligament through bone in adult rats. The roughness at the tendon insertion is probably due ... [more ▼]

We highlighted a morphological protrusion facilitating load transmission from the Achilles tendon to the plantar ligament through bone in adult rats. The roughness at the tendon insertion is probably due to mineralization gradients within fibrocartilage and may enhance interface toughness. Despite the low porosity and consequently high rigidity of the tuberosity, this region contains anisotropic pores likely oriented to minimize peak stresses. Our results suggest that not only the interface but also the underlying bone is well-adapted to accommodate tendon loading. [less ▲]

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See detailInfOPAL_Les actes du Colloque_De l'engagement des chercheurs au service de l'animal et de la recherche
Drion, Pierre ULiege; Tirelli, Ezio ULiege; Geris, Liesbet ULiege et al

in OPAL (Ed.) Les actes du Colloque (2018, October 19)

Le débat en matière d’expériences sur animaux porte, par essence, sur des valeurs qui ont, par définition, une forte connotation subjective. Il pourrait sembler par exemple que les commissions d’éthique ... [more ▼]

Le débat en matière d’expériences sur animaux porte, par essence, sur des valeurs qui ont, par définition, une forte connotation subjective. Il pourrait sembler par exemple que les commissions d’éthique animales doivent partir du principe que les intérêts de l’homme (ou d’une espèce animale) pèsent plus lourd que les intérêts des animaux d’expérience (Nicks B, note de cours). En aucun cas cependant dans une mesure telle que tout intérêt de l’homme (ou d’une espèce animale) prévale sur n’importe quel intérêt de l’animal… [less ▲]

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See detailLe bien-être animal dans le paysage éthique et réglementaire actuel : compte rendu d'expérience
Drion, Pierre ULiege

Conference (2018, October 19)

Ce colloque est axé sur le bien-être de l’animal de laboratoire au cours de la réalisation des projets de recherche : Gestion et suivi des écarts entre les projets autorisés et leur mise en œuvre ... [more ▼]

Ce colloque est axé sur le bien-être de l’animal de laboratoire au cours de la réalisation des projets de recherche : Gestion et suivi des écarts entre les projets autorisés et leur mise en œuvre. Amélioration continue : capitalisation sur l’expérience acquise. Responsabilités individuelles et collectives. Exploitation des appréciations rétrospectives. Ce colloque traite principalement des différentes actions de l'OPAL en faveur des méthodes alternatives et des outils mis en œuvre dans différents établissements pour s'assurer de l'adéquation des procédures mises en œuvre par rapport au projet validé d'un point de vue éthique et autorisé. [less ▲]

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See detailEccentric training for tendon healing after acute lesion: a rat model
Kaux, Jean-François ULiege; Libertiaux, Vincent; Leprince, Pierre ULiege et al

in Towards healthy tendon ageing... (2018, September)

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See detailPlatelet-Rich Plasma (PRP) and tendon healing: comparison between fresh and frozen-thawed PRP
Kaux, Jean-François ULiege; Libertiaux, Vincent; Dupont, Laura ULiege et al

in Towards healthy tendon ageing... (2018, September)

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See detailExpérimentation animale: la recette d'une polémique scientifique
Muraille, Eric; de kerchove, Alban; Muylkens, Benoit et al

Article for general public (2018)

La majorité du grand public accepte l’expérimentation animale à condition que celle-ci contribue à l’amélioration de la santé humaine et qu’aucune autre alternative n’existe. En face, les opposants ... [more ▼]

La majorité du grand public accepte l’expérimentation animale à condition que celle-ci contribue à l’amélioration de la santé humaine et qu’aucune autre alternative n’existe. En face, les opposants décrédibilisent la recherche et stigmatise une profession à des fins idéologiques. Relevé de leurs arguments. [less ▲]

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See detail"Enfin un code du bien-être animal pragmatique"
De Pape; Drion, Pierre ULiege

Article for general public (2018)

"Fin de semaine dernière, le Gouvernement wallon a adopté le Code du Bien-être animal, proposé par le ministre Carlo Di Antonio (cdH). Le texte sera prochainement soumis au Conseil d’Etat, poursuivant ... [more ▼]

"Fin de semaine dernière, le Gouvernement wallon a adopté le Code du Bien-être animal, proposé par le ministre Carlo Di Antonio (cdH). Le texte sera prochainement soumis au Conseil d’Etat, poursuivant ainsi son parcours législatif en vue de son adoption définitive. Le ministre applaudit « une première en Europe ». Les milieux académiques ont de leur côté émis un satisfecit sous réserve des arrêtés d’exécution sur cette 4e mouture. La mouture originelle de 2017 aurait signé selon eux et à moyen terme l’arrêt de l’expérimentation sur animaux de laboratoire en Wallonie." [less ▲]

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See detailLa souris, le patient, et le faux expert. Décryptage d'une mystification.
Bakker, Julie ULiege; Balthazart, Jacques ULiege; Baron, Frédéric ULiege et al

Article for general public (2018)

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les ... [more ▼]

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les contrôles qui y sont associés induisent de nombreuses contraintes pratiques, des charges administratives et des coûts financiers importants que les chercheurs seraient certainement heureux d'éviter s'il existait une alternative à l'expérimentation animale. [less ▲]

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See detailL'expérimentation animale ne se fait pas en dehors de tout contrôle (OPINION)
Muraille, Eric; de Kerchove d'Exaerde, Alban; Blanpain, Cedric et al

Article for general public (2018)

Proposer de réduire l'expérimentation animale pour raisons morales est louable. Mais ce choix de société ne doit pas être vendu au citoyen en lui laissant croire que la recherche conserverait la même ... [more ▼]

Proposer de réduire l'expérimentation animale pour raisons morales est louable. Mais ce choix de société ne doit pas être vendu au citoyen en lui laissant croire que la recherche conserverait la même qualité ou en serait améliorée. [less ▲]

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