Zebrafish Model

Key regulators of bone formation are highly conserved between mammals and teleosts. The corresponding orthologs share significant sequence similarities and an overlap in expression patterns when compared to mammals.

Cranial cartilage is the first skeletal structure to be detected as early as 3 days post-fertilization, while first calcified intramembranous bone structures start to form at about the same time.

Due to its rapid generation time, large offspring numbers, external development, transparency and the availability of genetic maps, the zebrafish is a very attractive model system to study the function of genes involved in bone formation.

Transgenic zebrafish lines represent unique tools to follow osteoblasts in vivo and to analyze their function in wild type or mutant backgrounds.

This animal model can be used to evaluate drug or treatment effects on cartilage and bone formation by measuring:

  • The intensity and progression of bone formation
  • Their level of ossification
  • The level of calcification
  • Morphometric analysis

Using this model, researchers from GIGA have evaluated the physiological consequences of altered gravity on bone formation and more generally on whole genome gene expression.

For more info on our zebrafish facility, click here.

Spontaneous osteoarthritis Guinea pig model

This guinea pig model mirrors the histopathological characteristics observed in human disease. The joint pathology in both guinea pig and human is age-related and linked to a diversity of risk factors such as body weight, mechanical load and high bone turnover. It is characterized by an early collagen fibril disruption occurring in articular cartilage, bone cysts, subchondral bone thickening and osteophytes are preceding histological proteoglycan loss and fibrillation.

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Osteoarthritis rabbit model

Osteoarthritis (OA) is a slowly progressing, degenerative disorder of synovial joints culminating in the irreversible destruction of articular cartilage and subchondral bone.

Acute anterior crucial ligament (ACL) injury has been shown to be a significant risk factor for the development of secondary OA.

In this model, OA is surgically induced by the transection of the ACL and offers herewith the opportunity to study the contributing factors (such as joint instability, changes in kinematics, and tissue degradative pathways) in the pathogenesis of OA following injury.

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Validated and qualified original biomarkers

We possess a collection of validated and qualified original biomarkers used for the monitoring of cartilage metabolism in animal models. In addition, these patented biomarkers are particularly useful for the follow-up of drug efficacy during the different development phases.

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Evaluation of mechanical properties

We use a Mach-1TM mechanical testing system, which allows ex vivo testing of cartilage biomechanical properties. The equipment is able to perform indentation, tension, shear and compression tests and mechanical stimulation on articular cartilage. This provides a complete characterization of cartilage mechanical properties and a 3D mapping.

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Mach-1-V500cst-450px

Evaluation of pain and lameness

Pain threshold and tolerance are measured using dolorimeters that apply well-defined steady pressure, heat or electrical stimulation to a specific area. It determines what level of heat, pressure, electric current or amount of movement produces a sensation of pain.

Lameness is evaluated using the CatWalkTM XT system, a highly sensitive tool to assess the gait and locomotion of small animals. For more info, click here.

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Preclinical GAIT analysis

The CatWalkTM XT system is a highly sensitive tool for quantitative assessment of footfalls and motor performance in unforced moving animals such as rats, mice and guinea pigs.

Catwalk Souris

It can be used to evaluate any experimental model/procedure that affects the locomotor ability of rodents (i.e. genetic, chemical, physical injury to the central nervous system, peripheral nervous system or skeletal or muscle functioning). More specifically, its use has been validated for spinal cord injury and other nerve injuries, neuropathic pain, arthritis, stroke, Parkinson’s disease, cerebellar ataxia, traumatic brain injury and peripheral nerve damage.

3D Analysis Catwalk

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Preclinical imaging

Logo_Logo-autres_GIGAOur GIGA platforms offer advanced preclinical functional and anatomical imaging solutions for a broad spectrum of application fields.

Our range of techniques includes:

Magnetic resonance imaging (MRI) scanners use strong magnetic fields and radio-waves to visualize detailed internal structures. Images are obtained in vivo with very high spatial and temporal resolution, good contrast for brain and soft tissues. MRI can be used in a wide variety of applications including anatomical, functional (fMRI) and molecular imaging for medical diagnosis, staging of disease and for follow-up without exposure to ionizing radiation.

Our system, Agilent MicroMRI 9,4T 310 ASR, is equipped with a technical imaging unit (MINERVE). It ensures the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

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Computed Tomography (CT) is a non-destructive technique that yields structural and anatomical high-resolution 3D images with limited or no sample preparation required. This imaging modality complements the metabolic or functional images obtained with PET.

Being equipped with two beds for mice (25 mm) and rats (75 mm), our system, the TriFoil Imaging eXplore CT 120 micro-CT, is designed to visualize, quantify and characterize anatomical parameters in small animals. The system is also equipped with a technical imaging unit (MINERVE), ensuring the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

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Positron Emission Tomography (PET) has the sensitivity at picomolar level to visualize molecular processes in 3D. In vivo PET imaging with labelled lead compounds will help to select the best one for clinical trials.

 

The technique allows:

  • The collection of quantitative and dynamic biodistribution data (e.g. micro-dosing studies) at an early stage of the clinical development: dynamic data for in-depth kinetic modeling, online blood measurements and in-brain positron-emission measurements
  • Detailed drug occupancy studies (proof of targets, mechanism, efficacy, pharmacokinetics, biodistribution)
  • Concentration analysis of targeted analytes after having developed and validated a dedicated method using microdialysis, a technique used for continuous measurement of free, bound analyte concentrations in the extracellular fluid. Analytes may include endogenous molecules (e.g. neurotransmitter, hormones, glucose, etc.) to assess their biochemical functions in the body, or exogenous compounds (e.g. pharmaceuticals) to determine their distribution within the body)

We are authorized to conduct research programs with classical (18F-FDG) and original radiotracers. Furthermore, we have developed expertise in experimental design, data collection, correction and modeling for kinetic analysis.

Being equipped with two beds for mice (25 mm) and rats (75 mm), our system, the Siemens Concorde FOCUS 120 micro-PET, is designed to visualize, quantify and characterize anatomical parameters in small animals. The system is also equipped with a technical imaging unit (MINERVE), ensuring the admission and extraction of anesthetic gas, thermoregulation of the study subject and monitoring of vital signs such as respiratory and cardiac frequencies.

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Our equipment includes the high-resolution, high-frequency ultrasound imaging system Vevo 2100 (Visualsonics). This is a non-invasive, in vivo micro imaging system, enabling visualization, assessment and measurement of anatomical structures and hemodynamic function in longitudinal studies for small animal phenotyping.

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The Xenogen IVIS 200 system is a highly sensitive and flexible system to trace bioluminescent reporter genes both in vivo and in vitro. It allows non-invasive longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in living animals. By performing spectral fluorescence imaging, it allows the simultaneous use of bioluminescence and fluorescence imaging.

Bioluminescence imaging uses the enzyme, luciferase, that can be inserted into the genome of cancer cells or the cells you wish to track. Once these cells are implanted within mice, a tail vein or intra-peritoneal injection of luciferin (luciferase substrate) allows to follow their distribution ex vivo without euthanasia.

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Intravital microscopy is an extremely powerful tool that enables imaging several biological processes in living animals. In particular, to analyze:

 

 

  • Recruitment processes of leukocytes and platelets on microvessel endothelia
  • Bacterial adhesion on the microvessel endothelia
  • Thrombi and vascular occlusion formation
  • Lymphocytes migration to lymph nodes and lymphocytes adhesion to endothelia

Our equipment includes a motorized Olympus Cell R (Upright) microscope with EMCCD camera, controlled via the Slidebook software.

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PXI X-RAD SmART Image Guided Irradiator combines 3D imaging with highly accurate radiotherapy for Small Animals: mice, rats and rabbits. It combines a user friendly interface with state-of-the-art Monte Carlo calculation algorithms to rapidly devise treatment plans.

The system is fully integrated, with automated CT-CT registration, allowing, Image Guided Radiotherapy for precise tumor/organ localization. The integrated treatment planning enables rapid and highly conformal radiotherapy treatments, with collimator from 1 mm to 10 cm in round and non-round shapes, to be delivered in any scenario, ranging from simple subcutaneous xenografts to complex metastatic models or to develop non tumoral model as radiation-induced injury for a specific purpose.

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