Thérapie par les cellules souches mésenchymateuses dans la guérison tendineuse chez le cheval

Les tendinites sont des lésions communes chez le cheval athlète, ayant un impact financier et sportif considérable. Les cellules souches mésenchymateuses (CSMs) de moelle osseuse (MO) sont empiriquement utilisées en clinique pour améliorer la guérison des affections myoarthrosquelettiques. Cependant, il est nécessaire de standardiser les protocoles d’isolement des CSMs équines et d’analyser leurs effets sur la guérison tendineuse pour ajuster leur dose. Les objectifs de cette étude étaient de comparer 3 méthodes d’isolement des CSMs équines et d’établir un modèle de guérison tendineuse minimal invasif pour analyser l’effet des CSMs sur cette guérison. Des CSMs de MO du sternum de juments étaient isolées par 3 protocoles couramment utilisés (adhérence au pétri (Classique) et 2 méthodes par gradient de densité (Percoll et Ficoll)). La viabilité des cellules après isolement, le rendement d’isolement, le nombre de CSMs obtenues après 14 jours de culture et leurs caractéristiques fonctionnelles (renouvellement et différentiation) étaient comparés entre les 3 protocoles. Les résultats suggéraient que le Percoll était le meilleur protocole en termes de rendement et de capacité de renouvellement des cellules. La différence n’était pas significative pour leur viabilité et leur capacité de différentiation. Un modèle de guérison tendineuse, consistant en une ténectomie du tendon extenseur latéral du doigt fut ensuite développé. Cependant, la grande variabilité interindividuelle de qualité de guérison dans le groupe pilote implique une ré-évaluation du modèle. Des études futures, avec des CSMs isolées par le Percoll dans de nouveaux modèles de guérison tendineuse devraient permettre de déterminer la dose adéquate de CSMs.In equine athletes, tendinitis lesions are common and lead to substantial financial losses. Bone marrow (BM) mesenchymal stem cells (MSCs) are employed clinically empirically to enhance healing of musculoskeletal injuries. However, there is a need to standardize equine MSC isolation protocols, to analyze the effects of MSCs on tendon healing and to optimize dosage. The objectives of the study were to compare 3 methods of equine MSC isolation and develop a minimally invasive model of tendon healing to analyze the effects of MSCs on tendon healing. BM MSCs from the sternum of mares were isolated by 3 protocols (adherence to a plastic culture dish (Classic) and two gradient density separation protocols (Percoll and Ficoll)) to compare for cell viability, MSC yield, number of MSCs attained after 14 days of culture and functional characteristics (self-renewal and multilineage differentiation) of the MSCs. The results suggested that the Percoll protocol was the best of those assessed in terms of MSC yield and self-renewal potential and that MSCs retrieved with the Ficoll protocol had the lowest self-renewal. There were no significant differences in terms of cell viability and differentiation capacity. A tendon healing model was then developed and consisted of a 0.5 cm tenectomy of the lateral digital extensor tendon. However, interanimal variation of healing quality was so high within the pilot group that the model should be re-evaluated. Further studies using MSCs isolated with Percoll in other novel models of tendon healing would allow determination of the adequate dosage of MSCs

A new comprehensive approach for bone remodeling under medium and high mechanical load based on cellular activity

The authors would like to thank the CNRS for its financial support through the Défi Mécanobiologie to carry out the work.Most of the last century, bone remodeling models have been proposed based on the observation that bone density is dependent on the intensity of the applied mechanical loads. Most of these cortical or trabecular bone remodeling models are related to the osteocyte mechanosensitivity, and they all have a direct correlation between the bone mineral density and the mechanical strain energy. However, experiments on human athletes show that high-intensity sport activity tends not to increase bone mineral density but rather has a negative impact. Therefore, it appears that the optimum bone mineral density would develop for “medium”-intensity activity (or medium mechanical loads) and not for the highest-intensity one

Effets comparatifs de protocoles de course sur la qualité et la réparation osseuse chez le rat Wistar

It is now well established that physical exercise has unquestionable beneficial effects on bone tissue and metabolism. However, no consensus regarding the osteogenic effects of exercise on healthy or healing bone has been reached yet. The objective of this work is (i) to evaluate the effects of two running protocols (continuous vs. intermittent) on the parameters of bone quality and bone metabolism, and (ii) to evaluate the preventive effects of these running protocols on bone repair in Wistar rats. We demonstrated here that high-intensity interval-running has positive effects on cortical bone quality, while moderate continuous running has beneficial effects on trabecular bone but is detrimental to cortical bone. These effects also depend on the bone (tibia vs. femur). In addition, our data suggest that both running protocols accelerate the repair of a non-critical bone defect in the tibia but not in the femur, possibly by modulating bone resorption. Associating different types of running is more beneficial to bone health than just one. As part of the refinement of animal models, the use of the tibia would be more suitable to study bone healing than the femurIl est désormais bien établi que la pratique d’un exercice physique a des effets bénéfiques sur le tissu osseux et son métabolisme. Cependant, aucun consensus n’a encore été établi en ce qui concerne les effets ostéogéniques de l’exercice sur l’os sain ou en cours de réparation. L’objectif de ce travail est d’une part d’évaluer les effets de deux protocoles de course (continue vs. Intermittente) sur les paramètres de la qualité osseuse et le métabolisme osseux, d’autre part d’évaluer les effets de la pratique préventive de ces protocoles de course sur la réparation osseuse chez le rat Wistar. Ces travaux mettent en évidence un effet bénéfique de la course intermittente avec intervalles de haute intensité sur la qualité de l’os cortical tandis que la course continue modérée a des effets bénéfiques sur la qualité de l’os trabéculaire mais néfastes sur l’os cortical. Ces effets dépendent également de l’os étudié (tibia vs. fémur). De plus, nos données suggèrent que les deux protocoles de course accélèrent la réparation d’un défaut osseux de taille non critique dans le tibia mais pas dans le fémur, probablement par modulation de la résorption osseuse. La pratique de différents types de course serait plus bénéfique à la santé osseuse qu’un seul. Dans le cadre du raffinement des modèles animaux, l’utilisation du tibia serait plus adaptée à l’étude de la guérison osseuse que le fému

Comparative effects of running protocols on bone quality and bone repair in Wistar rats

Il est désormais bien établi que la pratique d’un exercice physique a des effets bénéfiques sur le tissu osseux et son métabolisme. Cependant, aucun consensus n’a encore été établi en ce qui concerne les effets ostéogéniques de l’exercice sur l’os sain ou en cours de réparation. L’objectif de ce travail est d’une part d’évaluer les effets de deux protocoles de course (continue vs. Intermittente) sur les paramètres de la qualité osseuse et le métabolisme osseux, d’autre part d’évaluer les effets de la pratique préventive de ces protocoles de course sur la réparation osseuse chez le rat Wistar. Ces travaux mettent en évidence un effet bénéfique de la course intermittente avec intervalles de haute intensité sur la qualité de l’os cortical tandis que la course continue modérée a des effets bénéfiques sur la qualité de l’os trabéculaire mais néfastes sur l’os cortical. Ces effets dépendent également de l’os étudié (tibia vs. fémur). De plus, nos données suggèrent que les deux protocoles de course accélèrent la réparation d’un défaut osseux de taille non critique dans le tibia mais pas dans le fémur, probablement par modulation de la résorption osseuse. La pratique de différents types de course serait plus bénéfique à la santé osseuse qu’un seul. Dans le cadre du raffinement des modèles animaux, l’utilisation du tibia serait plus adaptée à l’étude de la guérison osseuse que le fémurIt is now well established that physical exercise has unquestionable beneficial effects on bone tissue and metabolism. However, no consensus regarding the osteogenic effects of exercise on healthy or healing bone has been reached yet. The objective of this work is (i) to evaluate the effects of two running protocols (continuous vs. intermittent) on the parameters of bone quality and bone metabolism, and (ii) to evaluate the preventive effects of these running protocols on bone repair in Wistar rats. We demonstrated here that high-intensity interval-running has positive effects on cortical bone quality, while moderate continuous running has beneficial effects on trabecular bone but is detrimental to cortical bone. These effects also depend on the bone (tibia vs. femur). In addition, our data suggest that both running protocols accelerate the repair of a non-critical bone defect in the tibia but not in the femur, possibly by modulating bone resorption. Associating different types of running is more beneficial to bone health than just one. As part of the refinement of animal models, the use of the tibia would be more suitable to study bone healing than the femu

Module informatique interactif sur le syndrome podotrochléaire du cheval

LYON1-BU Santé (693882101) / SudocSudocFranceF

Physical Activity and Bone Vascularization: A Way to Explore in Bone Repair Context?

International audiencePhysical activity is widely recognized as a biotherapy by WHO in the fight and prevention of bone diseases such as osteoporosis. It reduces the risk of disabling fractures associated with many comorbidities, and whose repair is a major public health and economic issue. Bone tissue is a dynamic supportive tissue that reshapes itself according to the mechanical stresses to which it is exposed. Physical exercise is recognized as a key factor for bone health. However, the effects of exercise on bone quality depend on exercise protocols, duration, intensity, and frequency. Today, the effects of different exercise modalities on capillary bone vascularization, bone blood flow, and bone angiogenesis remain poorly understood and unclear. As vascularization is an integral part of bone repair process, the analysis of the preventive and/or curative effects of physical exercise is currently very undeveloped. Angiogenesis-osteogenesis coupling may constitute a new way for understanding the role of physical activity, especially in fracturing or in the integration of bone biomaterials. Thus, this review aimed to clarify the link between physical activities, vascularization, and bone repair

Prediction of Cortical Bone Thickness Variations in the Tibial Diaphysis of Running Rats

International audienceA cell-mechanobiological model is used for the prediction of bone density variation in rat tibiae under medium and high mechanical loads. The proposed theoretical-numerical model has only four parameters that need to be identified experimentally. It was used on three groups of male Wistar rats under sedentary, moderate intermittent and continuous running scenarios over an eight week period. The theoretical numerical model was able to predict an increase in bone density under intermittent running (medium intensity mechanical load) and a decrease of bone density under continuous running (higher intensity mechanical load). The numerical predictions were well correlated with the experimental observations of cortical bone thickness variations, and the experimental results of cell activity enabled us to validate the numerical results predictions. The proposed model shows a good capacity to predict bone density variation through medium and high mechanical loads. The mechanobiological balance between osteoblast and osteoclast activity seems to be validated and a foreseen prediction of bone density is made available

Preventive Moderate Continuous Running-Exercise Conditioning Improves the Healing of Non-Critical Size Bone Defects in Male Wistar Rats: A Pilot Study Using µCT.

Although physical exercise has unquestionable benefits on bone health, its effects on bone healing have been poorly investigated. This study evaluated the effects of preemptive moderate continuous running on the healing of non-critical sized bone defects in rats by µCT. We hypothesized that a preemptive running exercise would quicken bone healing. Twenty 5-week-old, male, Wistar rats were randomly allocated to one of the following groups ( = 10): sedentary control (SED) or continuous running (EX, 45 min/d, 5 d/week at moderate speed, for 8 consecutive weeks). A 2 mm diameter bone defect was then performed in the right tibia and femur. No exercise was performed during a 4 week-convalescence. Healing-tissue trabecular microarchitectural parameters were assessed once a week for 4 weeks using µCT and plasma bone turnover markers measured at the end of the study protocol (time point T12). At T12, bone volume fraction (BV/TV; BV: bone volume, TV: tissue volume) of the healing tissue in tibiae and femurs from EX rats was higher compared to that in SED rats ( = 0.001). BV/TV in EX rats was also higher in tibiae than in femurs ( < 0.01). The bone mineral density of the healing tissue in femurs from EX rats was higher compared to that in femurs from SED rats ( < 0.03). N-terminal telopeptide of collagen type I in EX rats was decreased compared to SED rats ( < 0.05), while no differences were observed for alkaline phosphatase and parathyroid hormone. The study provides evidence that preemptive moderate continuous running improves the healing of non-critical sized bone defects in male Wistar rats