KaLy-Cell: Hepatocytes and Toxicology
Your hepatocyte partner
KaLy-Cell (member of GBA Group) has been developing its expertise in liver-related ADME-toxicology, ex-vivo and particularly in-vitro with hepatocytes, for almost 20 years.
Our services deliver information with hepatocytes and/or liver subcellular fractions to evaluate inter-species differences and inter-individual variability in xenobiotic safety and drug efficacy, and to explain mode of actions and adverse reactions. The information is helping in optimizing the discovery, development and approval of drugs, food additives, agrochemicals and nutraceuticals.
KaLy-Cell is actively involved in innovative research in hepatocyte cell biology and in-vitro ADME-toxicology. In addition to standard protocol-driven studies we also offer consultation service experience and customized studies.
Our Services
- Highly reproducible and accurate data, validated and used by pharmaceutical, biotechnology, agrochemical and cosmetics companies, and academic organizations.
- Data delivered within a short turnaround time of few weeks after receipt of the compounds, to fit in with the make-test timelines of drug discovery. Multiple reporting formats are available to suit your needs.
- Attention to good quality customer care, with highly trained scientists on hand to interpret results and recommend the most appropriate experimental strategy.
- Flexible and customized services, with studies tailored to meet customers’ specific requirements.
- Compliance with regulatory guidelines, ensuring consistent confidence in the data.
In-Vitro Enzyme Induction Studies
Enzyme induction can increase the metabolic clearance of co-administered drugs, potentially reducing their efficacy. As such, regulatory agencies such as the FDA or EMA recognize enzyme induction as a potential cause of drug-drug interactions.
We provide in-vitro screening enzyme induction studies using cryopreserved primary hepatocytes from various species (including human), as well as in vitro regulatory drug-drug interaction studies using cryopreserved primary human hepatocyte cultures, conducted in compliance with FDA, EMA, and ICH guidelines. While primarily focused on evaluating the potential induction of major human phase I CYP450 isoforms, we also assess key human phase II (UGT and SULT) and transporters (PGP, MDR2, BSEP) isoforms.
In-vitro screening for CYP induction
- Exposure of plated cryopreserved primary hepatocytes from various species (human, monkey, dog, minipig, rat and mouse).
- Parallel exposure with positive (reference inducers) controls to ensure test system responsiveness.
- Daily exposure for 1 up to 7 days.
- Induction assessment based on changes in gene expression via RT-qPCR.
- Comprehensive data summary.
In-vitro regulatory (FDA/EMA/ICH) CYP induction
- Exposure of plated cryopreserved primary human hepatocytes (from 3 donors), pre-characterized for response to positive control inducers, including for CYP Relative Induction Score (RIS).
- Parallel exposure with positive (reference inducers) and negative controls to ensure test system responsiveness.
- Daily exposure for 48h (mRNA expression levels) or 72h (enzyme activities).
- Induction assessment based on changes in gene expression via RT-qPCR.
- Enzyme activity determined by incubating hepatocyte monolayers with CYP-specific substrates and measuring CYP specific products by LC/MS (performed by a member of the GBA Group).
- Calculations: fold of control, % of positive control, EC50 and Emax determination and RIS score when possible.
- Exposure of hepatocytes to parent drug also measured by LC/MS (performed by a member of the GBA Group).
- Full data reporting.
In-vitro phase II UGT and/or SULT and transporters induction
- Exposure of plated cryopreserved primarycryopreserved hepatocytes from various species (human, monkey, dog, minipig, rat and mouse).
- Parallel exposure with reference inducers to ensure test system responsiveness.
- Daily exposure for up to 7 days in a sandwich culture configuration (see our publication Parmentier et al. 2017).
- Induction assessment based on changes in gene expression via RT-qPCR.
- Calculations: fold of control, EC50 and Emax determination when possible.
- Full data reporting.
In-vitro & Ex-vivo Metabolic Stability & Metabolite Identification
We provide in-vitro & ex-vivo metabolic stability and metabolite identification studies of xenobiotics and drug candidates. These analyses compare metabolic stability profiles or metabolite identification formed by human and animal species to identify the most relevant animal model for pharmacokinetic and/or toxicity studies.
- Ex-vivo, using animal and human liver subcellular fractions
- In-vitro, using cryopreserved primary hepatocytes from various species (human, monkey, dog, minipig, rat and mouse):
- in suspension under continuous shaking for short-term exposure,
- or plated and incubated for up to 7 days allowing short or long-term exposure
- Parallel incubations with marker substrates to ensure metabolic competency.
- Measurements at multiple time-points the concentration of parent compound and/or metabolites by HPLC/MS (performed by a member of the GBA Group).
- Calculations: Half-life, in-vitro/intrinsic clearance (metabolic stability) and proposed metabolic pathway (metabolite identification)
- Comprehensive data summary/full data reporting
In-vitro and Ex-vivo Acute and Chronic Liver-related Toxicities
We provide in-vitro and ex-vivo read outs of acute and chronic liver toxicity such as induction, repression or inhibition of major liver phase I and phase II metabolic enzymes (CYP450, UGTs…) using RT-qPCR for gene expression and LC-MS detection for enzyme activities (performed by a member of the GBA Group)
- In-vitro, using cryopreserved primary hepatocytes from various species (human, monkey, dog, minipig, rat and mouse) exposed for up to 7 days in a sandwich culture configuration allowing long-term culture and incubation
- Ex-vivo, using liver subcellular fractions from animals of toxicology studies
In the context of improving the detection of non-genotoxic carcinogens, we offer an in-vitro cell proliferation assay using plated cryopreserved primary hepatocytes from various species (mouse, rat and human). This assay supports the identification of compounds that may induce cancer through non-genotoxic mechanisms, helping to strengthen early safety evaluations.
We provide support in assessing liver-mediated toxic liabilities of xenobiotics through a panel of different in-vitro or ex-vivo evaluations. We use cryopreserved primary hepatocytes or hepatic subcellular fractions from various species (human, monkey, dog, minipig, rat and mouse) with studies tailored to address specific customer needs or customized issues.
In-vitro and Ex-vivo Drug induced liver injury (DILI)
We provide in-vitro and ex-vivo read outs of Drug Induced Liver Injury (DILI) prediction services by measuring separately, or combining the endpoints listed below:
- Cell viability – in-vitro: General cell viability assessment using single endpoints such as mitochondrial resazurin metabolism, LDH release or ATP content using cryopreserved primary hepatocytes from different species up to 7 days of incubation
- Oxidative stress – in-vitro & ex-vivo: To address hepatic disorders of detoxification pathways
- Steatosis – in-vitro & ex-vivo: To address hepatic lipid processing disorder, leading to accumulation of triglycerides within the liver cells
- Cholestasis – in-vitro: To address bile acid homeostasis disorder in cryopreserved primary hepatocytes from human or rat, leading to bile acid accumulation within liver cells, by determining a Drug-Induced-Cholestasis Index (DICI)
In-vitro Thyroid Related Endocrine Disruption Assays
The European Food Safety Authority (EFSA) and the European Chemicals Agency (ECHA) have implemented requirements mandating evidence of the absence of endocrine-disrupting potential for human health of all active substances in pesticides and biocides during regulatory submission or re-submission processes.
We provide non-GLP and GLP-certified in-vitro assays to evaluate chemicals for direct thyroid disruption including targets involved in thyroid hormone synthesis (NIS and TPO) and T4 activation and catabolism in tissue (DIO1, 2, 3). These inhibition assays enable cross-species comparisons and investigate different mechanisms of endocrine modulation, helping to evaluate the relevance of in-vivo toxicology findings.
- Sodium/Iodide symporter (NIS) inhibition assay: measures the uptake of iodide into HEK293 stably transfected cells ectopically expressing rat or human NIS, using the Sandell-Kolthoff (SK) reaction. A cell viability is performed in parallel to ensure proper interpretation of the inhibition data.
- Thyroperoxidase (TPO) inhibition assay: assesses TPO activity in rat or human thyroid microsomes by measuring the oxidation of the Amplex UltraRed (AUR) in the presence of H2O2.
- Deiodinases (DIO1, DIO2 and DIO3) inhibition assays: assess DIO1, DIO2 or DIO3 activities, in cell pellets from recombinant HEK293 cells ectopically expressing rat or human DIO1, DIO2 or DIO3, using HPLC-HRMS to quantify the T3 or the rT3 formed after addition of T4 substrate (performed by a member of the GBA Group).
- Parallel incubations with positive and negative controls to ensure test system responsiveness.
- Calculations: IC50 determination (when applicable, i.e., sufficient inhibition is observed). See our publication: Asselin, et al., 2024
We provide in-vitro and ex-vivo assays to evaluate indirect thyroid disruption such as in-vitro comparative liver enzyme induction assays to identify modulators of T4 catabolic pathways.
In-vitro using plateable cryopreserved primary hepatocytes from various species (rat, human, dog or mouse), pre-characterized for their response to CYP reference inducers. This assay investigates the species-specific differences in responses to liver enzyme inducers and their effect on thyroid hormone metabolism and clearance.
Daily exposure for 7 days in a sandwich culture configuration, allowing long-term exposure.
- Induction assessment based on changes in hepatic Phase I and Phase II gene expression via RT-qPCR.
- Liver specific enzyme activity determined by incubating hepatocyte monolayers with T4 and/or CYP-specific substrates. Resulting UGT-T4- and/or CYP-specific products are quantified by LC/MS (performed by a member of the GBA Group)
- T4 clearance and T4 metabolite formation (T4-Glucuronide, T4-Sulfate and T3/rT3) assessed over 24h and quantified using HPLC-HRMS*
- Parallel exposure with reference liver inducers to ensure test system responsiveness.
- Full data reporting
See our publications: Baze, et al., 2024; Baze et al., 2025 and case studies Walter et al., 2024; Wiemann et al, 2023, Parmentier et al., 2022
- Ex-vivo using liver subcellular fractions from animals of toxicology studies:
- Induction assessment based on changes in hepatic Phase I and Phase II gene expression via RT-qPCR.
- Liver specific enzyme activity determined by incubating T4 and/or CYP-specific substrates. Resulting UGT-T4- and/or CYP-specific products are quantified by LC/MS (performed by a member of the GBA Group)
- Full data reporting
Kaly-Cell
Contact us!
To learn more about us and what we can do for you please contact us.
E-mail: c.parmentier@kaly-cell.com
About KaLy-Cell
KaLy-Cell has been developing its expertise in in vitro ADME-Toxicology with hepatocytes for almost 20 years.
As a result KaLy-Cell is helping in optimizing the discovery, development and approval of drugs, food additives, agrochemicals and nutraceuticals.
KaLy-Cell is actively involved in innovative research in hepatocyte cell biology and in-vitro toxicology. In addition to standard protocol-driven studies we also offer consultation service experience and customized studies. In support of this type of research, we offer liver cellular products from animal and human origin.
GBA Group Pharma-Standorte
Mit dem Laden des Contents akzeptieren Sie die Datenschutzbestimmungen der GBA Group.
Mehr erfahrenKaLy-Cell
KaLy-Cell
20a Rue du Général Leclerc
67115 Plobsheim
Frankreich
Fax +333 88 43 56 71
Google Maps
Member of GBA Group since 2022