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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 (in press)

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 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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See detailAnalyse détaillée de la seconde version de l’avant-projet de Code du bien-être animal wallon. Lecture commentée au 21/03/2018 du Chapitre 8 (Expérimentation animale)
Drion, Pierre ULiege; Corhay, Albert ULiege; Haubruge, Eric ULiege et al

Report (2018)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984 et ses modifications, aujourd’hui, le projet de code pour la Région wallonne). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la Directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

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See detailEffects of Allogeneic Platelet-Rich Plasma (PRP) on the Healing Process of Sectioned Achilles Tendons of Rats: A Methodological Description
Greimers, Laura; Drion, Pierre ULiege; Colige, Alain ULiege et al

in Journal of Visualized Experiments (2018), 133

This article describes the experimental procedures used to observe if PRP can positively affect tendon healing. There are 4 main steps to follow: induce a lesion in the Achilles tendon; prepare PRP and ... [more ▼]

This article describes the experimental procedures used to observe if PRP can positively affect tendon healing. There are 4 main steps to follow: induce a lesion in the Achilles tendon; prepare PRP and inject it (or the saline solution); remove the tendon; and perform biomechanical, molecular, and histological evaluations. At each step, all the procedures and methods are described in detail, so they can be reproduced easily. Achilles tendons have been surgically sectioned (removal of a 5-mm long section). Afterwards, PRP or saline solution was injected to study whether PRP has a positive effect on the healing of the tendon. Three groups of 40 animals (a total of 120 rats were used in this study) were subdivided into 2 subgroups: PRP injection group and a saline injection control group. Rats were sacrificed at increasing time points (Group A: 5 days; Group B: 15 days; Group C: 30 days) and tendons were removed. 90 tendons underwent biomechanical testing before performing transcriptomic analysis and the 30 remaining tendons were submitted to histological analysis. [less ▲]

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See detailInterview Radio Expérimentation animale_ RTBF_ 03 février 2018
Drion, Pierre ULiege

Diverse speeche and writing (2018)

L'interview débute à la minute 6 et 40 secondes http://www.rtbfradioplayer.be/radio/liveradio/vivacite?rpAodUrl=http://rtbf-pod.l3.freecaster.net/rod/rtbf/geo/open/N/N3EidVLfcI.mp3&rpSt=12&rpSrp=2.0

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See detailL’expérimentation animale reste indispensable (OPINION)
Amorim, Christiani; Andris, Fabienne; Arckens, Lut et al

Article for general public (2017)

Trop fréquemment, l’expérimentation animale est présentée comme une pratique archaïque. Elle a bien changé. Et 100 % des patients traités le sont grâce aux concepts et techniques développés grâce à elle.

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See detailCommissions d’Ethique et Bien Etre Animal
Drion, Pierre ULiege

Scientific conference (2017, November 09)

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See detailAvant-projet de décret relatif au Code wallon du Bien-être des animaux Lecture commentée au 04 juillet 2017 des chap. 4, 8, 11
Drion, Pierre ULiege; Seutin, Vincent ULiege; Balthazart, Jacques ULiege et al

Report (2017)

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par ... [more ▼]

La compétence « bien-être animal », auparavant fédérale, a été régionalisée en juillet 2014. Ce projet de code vise à remplacer les dispositions légales en vigueur (la Loi de 1984 telle que modifiée par les décrets du Gouvernement wallon). Certains éléments sont repris tels quels de la Directive 2010/63. Cela est nécessaire car la Directive européenne en tant que telle n’a pas de force obligatoire en Belgique. Elle doit être transcrite par un instrument législatif (avant, la Loi de 1984, aujourd’hui, le projet de code). Certains aspects semblent flous, mais renvoient à des dispositions que le Gouvernement doit encore prendre (au travers d’arrêtés du Gouvernement wallon, comme le faisaient avant les nombreux arrêtés royaux et du gouvernement qui réglementent la matière). Les arrêtés d’exécution devront obligatoirement tenir compte de la directive européenne et s’inspirer de dispositions actuellement en vigueur. [less ▲]

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

in American Journal of Sports Medicine (2017), 45(6), 1440-1446

BACKGROUND:The tendon is a dynamic entity that remodels permanently. Platelet-rich plasma (PRP) injection has been shown to have a beneficial effect on tendon healing after lesion in rats. Furthermore ... [more ▼]

BACKGROUND:The tendon is a dynamic entity that remodels permanently. Platelet-rich plasma (PRP) injection has been shown to have a beneficial effect on tendon healing after lesion in rats. Furthermore, eccentric exercise seems to improve the mechanical quality of the tendon. HYPOTHESIS:A combination of PRP injection and eccentric training might be more effective than either treatment alone. STUDY DESIGN:Controlled laboratory study. METHODS:Adult male rats were anesthetized, an incision was performed in the middle of their left patellar tendon and an injection of physiological fluid (PF) or homologous PRP was randomly made at the lesion level. The rats were then divided into 2 groups: the eccentric group, undergoing eccentric training 3 times a week, and the untrained group, without any training. Thus, 4 groups were compared. After 5 weeks, the tendons were removed and their ultimate tensile strength and energy were measured. Tendons were frozen for proteomic analyses when all biomechanical tests were completed. Statistical analysis was performed with linear mixed effect models. RESULTS:No significant difference was found between the treatments using PF injection or PRP injection alone. However, the value of the ultimate tensile force at rupture was increased by 4.5 N (108% of control, P = .006) when eccentric training was performed. An intragroup analysis revealed that eccentric training significantly improved the ultimate force values for the PRP group. Proteomic analysis revealed that eccentric training led to an increase in abundance of several cytoskeletal proteins in the PF group, while a decrease in abundance of enzymes of the glycolytic pathway occurred in the PRP treated groups, indicating that this treatment might redirect the exercise-driven metabolic plasticity of the tendon. CONCLUSION: Eccentric training altered the metabolic plasticity of tendon and led to an improvement of injured tendon resistance regardless of the treatment injected (PF or PRP). CLINICAL RELEVANCE:This study demonstrates the necessity of eccentric rehabilitation and training in cases of tendon lesion regardless of the treatment carried out. [less ▲]

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See detailAccurate Control of 17beta-Estradiol Long-Term Release Increases Reliability and Reproducibility of Preclinical Animal Studies.
Gérard, Céline ULiege; Gallez, Anne ULiege; Dubois, Charline ULiege et al

in Journal of Mammary Gland Biology and Neoplasia (2017), 22(1), 1-11

Estrogens are the subject of intensive researches aiming to elucidate their mechanism of action on the various tissues they target and especially on mammary gland and breast cancer. The use of ready-to ... [more ▼]

Estrogens are the subject of intensive researches aiming to elucidate their mechanism of action on the various tissues they target and especially on mammary gland and breast cancer. The use of ready-to-use slow releasing devices to administer steroids, especially estrogens, to small experimental animals remains the method of choice in terms of animal well-being and of safety for both the researcher and the animal. In this study, we evaluated and compared, in vitro and in vivo, the release kinetic of estradiol (E2) over sixty days from two different slow-releasing systems: the matrix pellet (MP) and the reservoir implant (RI). We compared the impact of these systems in three E2-sensitive mouse models : mammary gland development, human MCF7 adenocarcinoma xenograft and mouse melanoma progression. The real amount of E2 that is released from both types of devices could differ from manufacturer specifications due to inadequate release for MP and initial burst effect for RI. Compared to MP, the interindividual variability was reduced with RI thanks to a superior control of the E2 release. Depending on the dose-dependent sensitivity of the physiological or pathological readout studied, this could lead to an improvement of the statistical power of in vivo experiments and thus to a reduction of the required animal number. Altogether, our data draw attention on the importance to adequately select the slow-releasing device that is the most appropriated to a specific experiment to better fulfill the 3Rs rule (Replacement, Reduction, Refinement) related to animal welfare and protection. [less ▲]

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See detailImmunomodulatory effects of rapamycin in xenogeneic Graft versus Host Disease
Ehx, Grégory ULiege; Hannon, Muriel ULiege; DUBOIS, Sophie ULiege et al

in Biology of Blood and Marrow Transplantation (2017, March), 23(3), 365366

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Several studies have suggested that rapamycin (RAPA), an mTOR ... [more ▼]

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Several studies have suggested that rapamycin (RAPA), an mTOR inhibitor with immunosuppressive properties, may reduce GVHD severity and mortality, possibly by promoting regulatory T cells (Tregs). However, few data have been reported about the impact of this drug on overall T cell population. The present work aims at investigating the mechanisms by which RAPA impacts GVHD in a humanized mouse model of GVHD (NSG mice infused with human PBMCs). We observed that RAPA injections significantly reduced xenogeneic GVHD lethality and severity. RAPA dramatically reduced human cells chimerism in RAPA mice and increased CD4+/CD8+ T cells balance due to a lower proliferation of CD8+ T cells. In addition, the frequencies of naive CD4+ and CD8+ T cells were higher and the CD4+ T cells showed a reduced effector phenotype (CD45RO+CD27-). Further, the differentiation of helper T cells (Th1, Th2 and Th17) was significantly decreased in treated mice. Tregs were positively affected as RAPA up-regulated their expression of BCL-2 and KI67 as well as their STAT5 phosphorylation level, leading to higher Treg frequency in treated mice. Altogether these data suggest that RAPA ameliorates GVHD by lowering cytotoxic and effector CD4+ T cells frequency as well as promoting Tregs. [less ▲]

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See detailAzacytidine prevents experimental xenogeneic graft-versus-host disease without abrogating graft-versus-leukemia effects
Ehx, Grégory ULiege; Fransolet, Gilles ULiege; De Leval, Laurence et al

in Oncoimmunology (2017)

The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading ... [more ▼]

The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) and graft-versus-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo. We observed that AZA improved both survival and xGVHD scores. Further, AZA significantly decreased human T-cell proliferation as well as IFN-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA significantly increased Treg frequency through hypomethylation of FOXP3i1 as well as increased Treg proliferation. The later was subsequent to higher STAT5 signaling in Treg from AZA-treated mice, which resulted from higher IL-2 secretion by conventional T cells from AZA-treated mice itself secondary to demethylation of the IL-2 gene promoter by AZA. Importantly, Tregs harvested from AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments. Finally, graft-versus-leukemia effects (assessed by growth inhibition of THP-1 cells, transfected to express the luciferase gene) were not abrogated by AZA. In summary, our data demonstrate that AZA prevents xGVHD without abrogating graft-versus-leukemia effects. These findings could serve of basis for further studies of GVHD prevention by AZA in acute myeloid leukemia patients offered an allogeneic transplantation. [less ▲]

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See detailLimited Impact of Imatinib in a Murine Model of Sclerodermatous Chronic Graft-versus-Host Disease
Belle, Ludovic ULiege; Fransolet, Gilles ULiege; Somja, Joan ULiege et al

in PLoS ONE (2016), 11

Background Sclerodermatous chronic Graft-versus-Host Disease (scl-cGVHD) is one of the most severe form of cGVHD. The Platelet-derived Grotwth Factor (PDGF) and the Transforming Growth Factor-β (TGF-β ... [more ▼]

Background Sclerodermatous chronic Graft-versus-Host Disease (scl-cGVHD) is one of the most severe form of cGVHD. The Platelet-derived Grotwth Factor (PDGF) and the Transforming Growth Factor-β (TGF-β) play a significant role in the fibrosing process occurring in scl-cGVHD. This prompted us to assess the impact of the PDGF-r and c-Abl tyrosine kinase inhibitor imatinib on scl-cGVHD. Methods To assess the impact of imatinib on T cell subset proliferation in vivo, Balb/cJ recipient mice were lethally (7 Gy) irradiated and then injected with 10x106 bone marrow cells from B10.D2 mice on day 0. Fourteen days later, 70x106 carboxyfluorescein succinimidyl ester (CFSE)-labeled splenocytes from B10.D2 mice were infused and imatinib or sterile water was administered for 5 days. To induce severe scl-cGVHD, Balb/cJ mice were injected i.v. with 10.106 bone marrow cells and 70.106 splenocytes from B10.D2 donor mice after 7 Gy irradiation. Mice were then given sterile water or imatinib from day +7 after transplantation to the end of the experiment (day +52). Results Imatinib decreased the proliferation of total T cells (P = 0.02), CD8+ T cells (P = 0.01), and of regulatory T cells (Tregs) (P = 0.02) in the spleen. In the severe scl-cGVHD model, imatinib-treated mice had significantly lower levels of PDGF-r phosphorylation than control mice on day 29 after transplantation (P = 0.008). However, scl-cGVHD scores were similar between vehicle- and imatinib-treated mice during the whole experiment, while there was a suggestion for less weight loss in imatinib-treated mice that reached statistical significance at day +52 following transplantation (P = 0.02). [less ▲]

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