Model of Dicer depletion in the otocyst

Previous studies have demonstrated the importance of Dicer during early cochlear development.

To extend this investigation to the establishment and differentiation of the prosensory domain, researchers at GIGA crossed Dicerflox/flox mice with FoxG1Cre/+ mice to generate embryos (i.e., FoxG1:Dicer-cKO) with an early (E8.5) depletion of Dicer in the otocyst.

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Ototoxic drug-treated animal

Typically, the cochlear effects of ototoxic drugs are studied in the guinea pig, which is the most common animal model used in hearing research.

In this model, guinea pigs receive an intrapritoneal injection of either Knamycin during 7 days or Cisplatin during 10 days.

Cisplatin- and aminoglycoside-induced ototoxicity is known to be mediated via injury to several terminally differentiated cellular targets in the cochlea, including the marginal and intermediate cells of the stria vascular.

To quantitatively assess hearing loss in toxic drug-treated animals, the Auditory Brainstem Responses (ABR) are measured weekly.

Contact [info@b2h.be] us to discuss how these capabilities can forward your projects! We will help you develop tailored solutions.

Guinea pigs deafened by aminoglycoside

Guinea pigs deafened by aminoglycoside are a model of neuronal degeneration secondary to hair cell destruction in the organ of Corti.

In this model, the left ear is operated on and the right ear is used as control (untreated ear, no operations). Each left bulla is opened under sterile conditions through a retro-auricular approach. The cochlea is exposed ventrally and opened using a 26 gauge needle. A catheter is inserted and connected to an electrical Hamilton syringe pump. The aminoglycoside gentamicin is administered at a concentration of 50 mg/ml for the cochlear lesion (25 ml of gentamicin in 5 min). Using the same cochlear opening, a catheter inserted and connected to a subcutaneous osmotic pump filled with products to be tested and dissolved in artificial perilymph solution.

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Cells regeneration

Researchers at GIGA have demonstrated that mammalian hair cells can be directly generated from supporting cells by inhibition of ephrin-B2 signaling.
Using either ephrin-B2 conditional knockout mice, shRNA-mediated gene silencing or soluble inhibitors, they found that downregulation of ephrin-B2 signalling at embryonic stages results in supporting cell translocation into hair cell layers and subsequent switch in cell phenotype from supporting cell to hair cell.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Role of ELP3

Elp3 lysine acetyl-transferase, the catalytic subunit of the Elongator complex, has been assigned multiple roles in gene transcription, DNA methylation and protein translation efficiency.

Given the importance of acetylation homeostasis in controlling developmental processes together with recent reports implicating Elp3 in cortical neurogenesis, researchers at GIGA investigated its role during inner ear formation.

Using different knock-out mouse models, they have shown that Elp3 enzyme is crucial for neuronal survival in the spiral ganglion and in the vestibule and that it ensures a correct innervation pattern in the developing inner ear. In the absence of Elp3, a drastic increase in the number of apoptotic neurons particularly during the early stages of development (between E12.5 and E14.5). Postnatally, the neurons remaining in Elp3cKO cochleae seem to establish synaptic contacts with the sensory cells but show obvious signs of cell damage.

Furthermore, they identified a severe hearing loss in Elp3cKO mice through Auditory Brainstem Response.

Taken together, these data support a role for Elp3 in hearing and balance and point out an important role for acetylation homeostasis during inner ear formation.

Interested in these projects? Drop us an email [info@b2h.be]. We are looking forward collaborating with you!

Stability testing

Stability testing is performed after storage in defined conditions according to standard and accelerated ICH conditions. We provide you with different range of storage conditions. All storage rooms are fully-controlled with 24/7 monitoring and alert systems.

Our services include:

  • Support in designing studies for real-time
  • Development and validation of “stability indicating methods”
  • Examination of stability-relevant parameters (temperature – humidity)
  • Interim reports for every testing period
  • Comprehensive final report

Looking for clinical advice or support, or preparing for a clinical study? We will help you set up a cost-effective and time-efficient study! Get in touch with our experts [info@b2h.be].

Drug administration & Patient monitoring

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  • Centralized clinical unit with 30 equipped hospital beds
  • Experience in running different study types and trial design
  • Different types of drugs like NCE and NBE
  • Database of more than 2.700 healthy and reliable volunteers
  • Privileged access to medical and technical expertise of CHU and ULg (such as Cyclotron, GIGA, CIP, Sleep Center, Pain clinic…)

We offer you a professional and scientific support to conduct clinical trials and the decision making processes during the early phases of the development of new molecules. This includes clinical pharmacology trials giving an insight into a drug candidate’s safety, tolerability, pharmacokinetics and pharmacodynamics.

Looking for clinical advice or support, or preparing for a clinical study? We will help you set up a cost-effective and time-efficient study! Get in touch with our experts [info@b2h.be].


Induced pluripotent cells

One team of the GIGA has developed an artificial sensory epithelia or “Mini Ear” in vitro model mimicking the in vivo organ equivalent.

For this purpose, otic progenitor cells (hOPCs) were generated using a reproducible protocol based on the differentiation of human induced pluripotent stem (hiPS) cells. Those hOPCs are at least 90% homogenous and can be frozen and thaw ad libitum. Those cells can be further differentiated towards inner ear hair cells using a stepwise method mimicking inner ear development.

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Bio-analysis

  • Standard biology analysis: certification for more than 550 tests, 17025 and 15189 ISO standards and BELAC accreditation
  • Development of personalized drug monitoring
  • Determination of IMP, metabolites and drug residues in different biological matrices
  • PK, PD and immunogenicity testing

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Looking for clinical advice or support, or preparing for a clinical study? We will help you set up a cost-effective and time-efficient study! Get in touch with our experts [info@b2h.be].

Preclinical imaging

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

Our range of techniques includes: