Image: A full-thickness punch biopsy from a patient with skin disease.
Our models provide invaluable insights for drug discovery and preclinical patient stratification. Here’s an in-depth look at our psoriasis and atopic dermatitis (AD) assays:
Atopic Dermatitis Disease Model Induced in Normal Skin
Our AD model is meticulously designed to simulate the inflammatory response characteristic of atopic dermatitis. Multiple (20+) biopsies are created from a single human skin specimen donated following surgery. A proprietary stimulation cocktail is used to induce the production of IL-5, IL-13, and IL-22 by the biopsies, replicating the cytokine profile observed in AD patients. The model’s responsiveness to steroid treatment validates its use as a control in evaluating new test articles. The availability of high numbers of biopsies from each donor, supports investigations across multiple test compounds or concentrations.
Psoriasis Phenotype Disease Model Induced in Normal Skin
To create a psoriasis-like phenotype in healthy human skin explants, we employ a test cocktail that activates the Th17/IL-17 pathway. By measuring changes in cytokine profiles or in gene expression post-incubation with your test article, we can assess the efficacy and safety of potential psoriasis treatments. This method allows high numbers of test conditions to be studied in skin biopsies isolated from each donor skin specimen.
Skin Models using Diseased Tissue from Patients with AD or Psoriasis:
Our test system using skin from patients with atopic dermatitis is the closest possible ex vivo model of disease biology. Patients volunteer to assist medical research by donating punch biopsies of inflamed areas of skin, which are rapidly transported to our laboratory for use in your customised experimental protocol.
- Targeted Diseased Tissues: We utilize tissues from patients diagnosed with psoriasis or atopic dermatitis, ensuring the disease biology is accurately reflected.
- Multiple Biopsies: For each donor, we obtain three biopsies, maximizing the data available for analysis.
- Donor Information: Detailed donor profiles enhance the pharmacological data, offering a comprehensive understanding of the test results.
- Disease Severity Scoring: We score disease severity, providing a quantitative measure to correlate with treatment efficacy.
- Preclinical Patient Stratification: Ideal for early-phase testing to identify patient subgroups likely to respond to specific therapies.
All of the above models involve culturing skin biopsies ex vivo, to retain the complex tissue architecture and relevance to the human condition, making our assays as predictive of patient responses as possible.
In many cases, our clients firstly test multiple compounds or concentrations via our higher throughput induced disease models where over 20 biopsies can be studied per donor (Phase 1 of the infographic), before progressing to test the effect of their compounds in biopsies from patients with psoriasis or atopic dermatitis (Phase 2).
Here’s a look at our human skin explant assay methodology.
Human Skin Explant Assay Methodology:
- Biopsy Collection: Multiple full-thickness biopsies (3 mm x 3 mm) are taken, encompassing the epidermis, dermis, and hypodermis.
- Day 0: Test compounds are introduced, and the media is changed to minimize biopsy-induced cytokine release.
- Day 1: Both test compounds and the differentiating test cocktail are added, followed by another media change.
- Day 2: Media is collected for phenotype analysis via ELISA, and biopsies are harvested for rtPCR.
Check out some key features of our services below, all designed to give you detailed insights into drug effects and mechanisms.
Comprehensive Testing and Analysis:
- Global Procurement Network: We source both healthy and diseased tissues globally, ensuring diverse and relevant sample sets.
- Customized Experimental Plans: Each test article is evaluated per a tailored experimental plan, with data analysis aligned with your specific requirements.
- Expert Reporting: Post-testing, we deliver a detailed report reviewed by our expert team. We provide thorough data summaries and interpretations, ensuring you are fully prepared for clinical trials.
- Fresh Tissue Biopsies: Our R&D team processes living human skin to create punch biopsies, ideal for testing your drug compounds.
- Gene expression by IHC, PCR or RNASeq: Changes in gene expression can readily be conducted on all our skin models.
- Cytokine Pathway Focus: Our assays can activate pathways like Th17/IL-17 in fresh skin explants to mimic disease conditions such as psoriasis.
- Multiplex Cytokine Analysis: We conduct multiplex analysis of multiple cytokines per tissue sample, facilitating detailed exploration of drug effects and mechanisms (recommended for induced disease models where higher numbers of biopsies are available per donor).
Advancing drug discovery has never been more efficient, thanks to our specialized models. We streamline the process, making it simpler and more effective to develop new treatments.
Advancing Drug Discovery:
- IL-17 Pathway Targeting: Our models are instrumental in the development of drugs, for example, by testing the efficacy of drugs targeting the IL-17 pathway, providing early proof of concept in humans.
- Gene Expression and Cytokine Production: By measuring changes in these areas, we evaluate how novel compounds interact with disease mechanisms.
- Mechanistic Insights: Our assays allow for the investigation of specific pathways and mechanisms, providing crucial data to inform the development of effective treatments.
REPROCELLS’s psoriasis and atopic dermatitis assays offer a robust platform for preclinical drug testing, ensuring your therapeutic candidates are thoroughly evaluated in clinically relevant models. Our commitment to detailed analysis and expert interpretation gives you the confidence needed to advance your drug discovery projects.
