Skin Disease Models

Modeling of skin diseases with reconstituted skin

To model skin diseases, we develop reconstituted skin models based on genetically modified, immortalized primary skin cells. Our disease models are suited to studying molecular disease mechanisms and evaluating the efficacy of therapeutic products and active substances. 

Infection models

are reconstructed epidermis and full-thickness skin models on whose stratum corneum pathogenic microorganisms trigger dermatological infections. 

Psoriasis models

are reconstructed epidermis and full-thickness skin models made from immortalized, genetically modified primary keratinocytes (overexpression of an exogenous STAT3 gene). Proinflammatory stimuli such as the addition of cytokines or the integration of T cells are used to trigger typical psoriasis characteristics in the skin model. The psoriasis models express characteristic protein markers (e.g. S100A7, CK16, IL-8) and exhibit morphological features such as thickening of the epidermis (acanthosis), impaired final differentiation of keratinocytes (parakeratosis) and thickening of the stratum corneum (hyperkeratosis). 

Histological sections of a skin model of healthy skin (a) compared to our 3D in vitro psoriasis model (b) and in vivo skin of a psoriasis patient (c). Disturbed differentiation of keratinocytes (parakeratosis), thickening of the epidermis (acanthosis) and the stratum corneum (hyperkeratosis) are typical of psoriatic skin.
© Fraunhofer IGB
Histological sections of a skin model of healthy skin (a) compared to our 3D in vitro psoriasis model (b) and in vivo skin of a psoriasis patient (c). Disturbed differentiation of keratinocytes (parakeratosis), thickening of the epidermis (acanthosis) and the stratum corneum (hyperkeratosis) are typical of psoriatic skin.

Skin disease models: effective in-vitro models for drug development as an alternative to animal testing

Challenge: (pre-)clinical research without animal testing

High failure rates in drug development are driving a paradigm shift in basic and preclinical research (Adhikary, P.P., Ul Ain, Q., Hocke, A.C. et al. COVID-19 highlights the model dilemma in biomedical research. Nat Rev Mater 6, 374–376 (2021), https://doi.org/10.1038/s41578-021-00305-z). Animal models do still represent the gold standard. However, they are limited by interspecies differences and the resulting poor prediction of human physiological and pathological conditions. To close this translational gap, human in-vitro disease models are increasingly being developed (Loewa, A., Feng, J.J. & Hedtrich, S. Human disease models in drug development. Nat Rev Bioeng 1, 545–559 (2023), https://doi.org/10.1038/s44222-023-00063-3).

These enable

  • to gain more precise and comprehensive scientific insights into the molecular mechanisms that underlie diseases,
  • to handle and repeat experiments easily with very good reproducibility and
  • to ensure a high relevance of the results by reproducing essential aspects of tissue and organ complexity. 

The use of suitable disease models in (pre-)clinical research increases the success rate of clinical implementation, reduces the costs of drug development and results in increasingly effective active ingredients (Loewa, A., Feng, J.J. & Hedtrich, S. Human disease models in drug development. Nat Rev Bioeng 1, 545–559 (2023), https://doi.org/10.1038/s44222-023-00063-3).

Our development: specific and complex 3D skin disease models

With our decades of experience in the development and targeted genetic modification of human cell lines, the establishment of human reconstituted 3D skin models and adherence to the highest quality standards, we establish specific disease models in complex three-dimensional structures that allow (inter-)cellular interactions. 

Unique selling point: disease models with high clinical relevance

Depending on the requirements and necessary complexity, our disease models are established from components of the skin, for example primary or immortalized primary fibroblasts and keratinocytes, immune cells, genetically modified cells and microorganisms.

Our disease models are highly comparable to the in-vivo situation of the patient. They therefore have high clinical relevance and very good predictability.

Immortalized primary cells guarantee that our skin models are donor-independent, reproducible and available at any time. Targeted genetic modification of cells allows diseases associated with defective protein function in particular to be transferred to in-vitro models. 

Application areas

In-vitro modeling of diseases is a central component of biomedical research in order to 

  • understand the basic molecular mechanisms of diseases,
  • to conduct efficacy studies in the preclinical development of pharmaceuticals and medical products, but also
  • to support product developments for skin care cosmetics, especially for diseased skin.

Services offer

We offer a wide range of services related to our disease models, which we carry out in modern laboratories on behalf of and in close cooperation with and for our customers:

  • Conducting studies, identifying targets and substance screenings 
  • Development of innovative and complex disease models including
    • Isolation of primary cells
    • Production of genetically modified cell lines (stable and transient)
    • Reporter cell lines with different intracellular and secreted reporters
    • 3D tissue reconstitution
    • Phenotypic and functional characterization of models, in particular with regard to disease-specific molecular markers
  • Dispatch of disease models

Analysis methods

Our disease models enable the investigation of molecular disease mechanisms and the effects of active ingredients and care products on the tissue architecture and physiological properties of the disease models. The analyses can be performed on the entire full skin model as well as separately in dermis and epidermis.

We offer the following analysis methods:

  • Vitality measurements, for example using the MTT test (colorimetric test), alamarBlueTM ...
  • Multiplex analysis for the detection and quantification of secreted proteins, such as cytokines, chemokines, growth factors and antimicrobial peptides
  • Histological and immunohistochemical staining of tissue thin sections
  • Protein analyses using Western blot and
  • RNA and DNA analyses using PCR or qPCR and sequencing

Reference projects

May 2020 – April 2022

Psoriceptors – endogenous immune receptors as targets for the treatment of psoriasis

 

In the "Psoriceptors" project, we have established a novel human 3D psoriasis skin model which mimicks the psoriasis-typical inflammatory reaction. Since toll-like receptors (TLR) play a role in the development of psoriasis the model is suited for screening for molecules with TLR inhibitory activity as potential active substances.

Duration: November 2019 – October 2022

PsoBiBi – development of psoriasis therapeutics using bicyclic genetically encoded libraries

 

Toll-like receptors (TLR) of the innate immune system play a key role in inflammatory skin diseases like psoriasis. In the PsoBiBi project, Fraunhofer IGB identifies, synthesizes and validates TLR antagonists for topical application as an alternative to conventional treatment methods, some of which have considerable side effects.