Selecting the most relevant skin model is crucial for the success of dermatological preclinical and translational research. Generating clear safety and dose-dependent efficacy data is essential for Investigational New Drug (IND) applications and advancing to clinical trials. Increasingly, regulators expect this data to be supported by human-centric testing models.
While in vitro systems and animal models are suitable for early-stage research and testing, limitations exist. Ex vivo tissue models are being recognized as the gold standard for dermatology drug development. By preserving the full biological complexity of human skin, ex vivo tissue models provide a more predictive platform for evaluating dermatological agents, helping to bridge the gap between early-stage testing and clinical trials.
What Are Ex Vivo Human Skin Tissue Models?
Ex vivo human skin tissues are living skin explants obtained from consenting donors following surgical procedures. Ex vivo models preserve the full tissue architecture and cellular diversity of human skin, including the epidermis, dermis, skin barrier, extracellular matrix, immune cells, hair follicles, and sebaceous glands. Because the tissue remains structurally intact, critical cell-to-cell and cell-to-matrix interactions are preserved, making ex vivo models highly representative of in vivo conditions.
“Ex vivo human skin tissues preserve the actual structural integrity and cell-to-cell signaling found in living organisms. This allows us to gather far more reliable data on how a compound interacts with the skin and influences human biology, significantly reducing the uncertainties inherent in transitioning from a lab setting to clinical trials.” Genemarkers’ scientist Stephanie Cunningham explains.
Bridging the Gap Between Preclinical Research and Clinical Outcomes In Dermatology Drug Development
One of the biggest challenges in early drug discovery and development is translating early-stage findings into clinical outcomes. Many drug candidates fail because early-stage data did not accurately predict safety and efficacy in human populations. Ex vivo models address this issue by enabling researchers to evaluate drug effects in intact human skin tissues before clinical trials begin.
“A major challenge in drug development is that works in in vitro or animal models doesn’t always translate to patients,” adds Cunningham. “Ex vivo tissues help close that gap by providing data in a system that more closely reflects human biology.”
By demonstrating how molecular and cellular changes translate into tissue-level responses, ex vivo models provide stronger evidence of safety and efficacy, reducing uncertainty and supporting more reliable decision-making prior to IND submissions or clinical trials.
Benefits of Ex vivo Tissue Models in Dermatology Preclinical and Translational Research
The growing adoption of ex vivo models is driven by their ability to deliver more predictive, human-centric data. Key advantages include:
- High physiological relevance
- Intact extracellular matrix and signaling networks
- Ethical alternative to animal testing
- Compatibility with multi-omic analysis
Ex Vivo Tissues Offer High Physiological Relevance
Dermatology drug development is uniquely dependent on tissue structure. The skin barrier, immune cells, and skin appendages all influence drug penetration and treatment response. Ex vivo models offer high physiological relevance by maintaining these features, allowing researchers to evaluate how a topical therapeutic or active pharmaceutical ingredient interacts with multiple cell types and layers simultaneously. This is not feasible in simpler 2D in vitro systems.
Extracellular Matrix and Cell Signaling Pathways Remain Intact in Ex Vivo Models
Extracellular matrix and cell-signaling pathways are intact in ex vivo models, replicating the native 3D tissue architecture and biological complexity of human skin. Because the extracellular matrix and cell-signaling pathways in ex vivo tissues closely resemble in vivo conditions, ex vivo models allow for a greater understanding of how a dermatologic agent influences key biological processes such as inflammation and tissue regeneration.
Ex Vivo Models as an Alternative to Animal Testing
Regulatory agencies are increasingly recognizing that safety and efficacy data generated in animal models may not always translate to human skin. By using living human skin tissue obtained from consenting donors, ex vivo tissue models align with regulatory and ethical standards while improving the predictive value of preclinical data.
Ex Vivo Tissues are Compatible with Multi-Omic Analysis
Ex vivo tissue models are well-suited for biomarker-based studies. By measuring changes in gene and protein expression in living tissue, drug developers get deeper insights into safety, efficacy, pharmacodynamics, pharmacokinetics, and mechanisms of action. Ex vivo tissue models can be paired with a range of testing technologies, including qPCR, RNA-Seq, ELISA, and Meso Scale Discovery (MSD).
Incorporating Ex Vivo Tissue Models into Dermatology Drug Development
Dermatology researchers have rapidly adopted the use of ex vivo tissues for drug discovery and development.
Applications of Ex Vivo Tissue Models in Dermatology Research Include:
- Atopic dermatitis and psoriasis drug development programs
- Inflammation and immunomodulation studies
- Topical and transdermal drug delivery research
- Safety and toxicity studies
- Wound healing and tissue regeneration research
Using Ex Vivo Tissues for Psoriasis and Atopic Dermatitis Drug Development
In drug development programs targeting skin conditions such as atopic dermatitis (AD) and psoriasis, ex vivo models support efficacy evaluation, mechanism of action studies, and investigation of tissue response in a human- and disease-relevant system.
Genemarkers offers ex vivo tissue models that mimic key components of AD and psoriasis. Our scientific team has verified the expression of over 30 AD-specific and 400 psoriasis-specific gene expression biomarkers in these tissue models. Our stimulated ex vivo tissue models are well-suited for generating preclinical safety and efficacy data in a human-relevant system.
Ex Vivo Tissue Models for Inflammation and Immunomodulation Studies
Ex vivo tissue models are highly valuable in inflammatory and immunomodulation studies. By maintaining the full tissue architecture, ex vivo tissues enable detailed analysis of cytokine signaling, pathway modulation and immune cell activation, allowing researchers to evaluate immune pathways, drug penetration and target engagement.
Measuring Topical and Transdermal Drug Delivery With Ex Vivo Models
For topical and transdermal drug delivery systems, ex vivo models allow for precise and accurate measurement of drug penetration, absorption, and retention across skin layers. This information is useful for evaluating formulation performance and optimizing delivery strategies.
Utilizing Ex Vivo Tissues for Safety and Toxicology Studies
In safety and toxicity studies, ex vivo systems facilitate early detection of irritation, cytotoxicity, and adverse tissue responses. By maintaining the natural skin tissue structure, human skin explants allow for accurate assessment of skin penetration, irritation, and any resulting damage, providing a human-relevant alternative to animal-based models.
Incorporating Ex Vivo Tissues in Wound Healing and Tissue Regeneration Research
Ex vivo tissue models are increasingly incorporated into wound healing and tissue regeneration research, where understanding how therapeutics affect tissue repair is essential for clinical success. Ex vivo tissue models provide data on inflammation, remodeling, and cytokine signaling to support wound healing research.
Genemarkers’ Ex Vivo Tissue Models for Dermatology Drug Development
Genemarkers offers a comprehensive portfolio of ex vivo human skin tissue models to support dermatology drug development from early research through clinical development. All tissues are sourced from consenting surgical donors, with flexibility in sex, ethnicity, age, and pigmentation. In addition to healthy tissue models, Genemarkers offers disease-state and stimulated ex vivo models. Our atopic dermatitis and psoriasis tissue models are supported by extensive molecular characterization, enabling deeper insight into disease pathways and treatment response.