In vitro models

Our portfolio

© K. Dobberke for Fraunhofer ISC

At the Fraunhofer TLC-RT, there is a broad portfolio of in vitro tissue models available for a wide variety of questions. Within our portfolio, we focus on barrier organs such as the skin, intestine, respiratory tract, or the blood-brain barrier. The models are of human origin and are generated either from primary cells or stem cells such as induced pluripotent stem cells. The aim is to make an active contribution to the reduction of animal experiments without neglecting the necessary efficacy testing or risk assessment. Hence, the TLC-RT commits itself to a high standardization of the models and industrial applicability to bridge the gap between academic and industrial research.


Besides the healthy state, we can also mimic diseased tissues to determine the efficacy of novel therapeutics in a fully human setting. Due to the high predictive capacity of the test systems, the risk of cost-intensive failures in the translation from the preclinical to the clinical phases can be minimized.

 

© K. Dobberke für Fraunhofer ISC

In-vitro Tumor
© Fraunhofer ISC
In-vitro laboratory
© Fraunhofer ISC

Your local contact

Florian Groeber-Becker

Contact Press / Media

Dr. Florian Groeber-Becker

Head of in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Neunerplatz 2
97082 Würzburg, Germany

Phone +49 931 31-86669

  • Send email
Christian Lotz

Contact Press / Media

Dr. Christian Lotz

Deputy head of in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-82596

Tissue models of the human conductive airways

In-vitro models Airways
© Fraunhofer ISC
Methylene blue staining of a 3D tissue model of the human airway mucosa

We generate 3D tissue models of the human nasal and tracheobronchial mucosa with high in vitro in vivo correlation using primary epithelial cells and biological scaffolds.

The epithelial cells differentiate to the mucociliary phenotype and are anchored to the connective tissue via a basement membrane. The tissue models can be used for example for risk assessment of biological and synthetic substances, infection studies and in the field of personalized therapy.

Services

  • Efficacy testing of new drug candidates
  • Risk assessment
  • Customer-specific development of new models and test procedures
  • Analysis of the ciliary beat by means of high-speed microscopy
  • Morphological / histological analyses of the tissue models
  • Analysis of cell viability, barrier integrity, gene and protein expression

Applications

  • Drug development for respiratory diseases
  • Infection studies with (human-pathogenic) viruses for the development of new drugs (e.g. SARS-CoV-2) in cooperation with Prof. Jochen Bodem (University of Wuerzburg)
  • Preclinical studies for drug candidates, formulations or nanoparticles
 

Research vs. Corona

Three-dimensional tissue models can be used to detect the mechanisms of infection by SARS-CoV-2 and allow new drugs to be tested without the need to use animal models. Thus, these models make an important contribution to the rapid response to pandemics. The models of the conducting airways developed at the TLZ could, for example, be infected with SARS-CoV-2 and are used in the Fraunhofer vs. Corona programme to identify drug candidates against SARS-CoV-2.

 

Your local contact

Maria Steinke

Contact Press / Media

Dr. Maria Steinke

Project leader in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-80720

Human 3D tissue models for infection studies

In-vitro infection model SARS-CoV-2
© Fraunhofer ISC
Airway tissue models infected with SARS-CoV-2

For many pathogens, humans are the only natural hosts. Here, the data collected from animal experiments are often not transferable to the mechanisms in the human organism. Together with our partners of the Research Training Group 2157, we investigate the interaction of human pathogens with the host tissue using appropriate 3D tissue models in vitro.

If we understand the key events of natural infections, we will be able to develop new preventive and therapeutic strategies to fight infectious diseases.

Services

  • Customer-specific development of new models and test procedures
  • Analysis of viral replication
  • Morphological / histological analyses of infected tissue models
  • Analysis of cell viability, barrier integrity, gene and protein expression

Applications

  • Elucidation of molecular infection mechanisms
  • Preclinical infection studies for drug candidates
  • Testing of therapeutic approaches
 

Research vs. Corona

Three-dimensional tissue models can be used to detect the mechanisms of infection by SARS-CoV-2 and allow new drugs to be tested without the need to use animal models. Thus, these models make an important contribution to the rapid response to pandemics. The models of the conducting airways developed at the TLZ could, for example, be infected with SARS-CoV-2 and are used in the Fraunhofer vs. Corona programme to identify drug candidates against SARS-CoV-2.

 

Your local contact

Maria Steinke

Contact Press / Media

Dr. Maria Steinke

Project leader in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-80720

Human tissue models of the eye for in vitro testing

In-vitro-Models Eye Cornea
© pixabay

The human eye is responsible for the optical perception of our environment. In order for light to reach the sensory cells of the retina, the eye is only protected by a thin and transparent tissue, the cornea. Compared to the epidermis of the skin, the cornea is not keratinized and is therefore more susceptible to mechanical and chemical injuries.

For this purpose we have developed a human cornea model as an alternative to animal experiments, which reflects the in vivo anatomy. Due to the central importance of our visual sense and its vulnerability, we offer standardized test protocols to assess the potential risk and efficacy of substances and wound healing for the human eye.

Services

  • Efficacy testing of topical and systemic drug candidates
  • Determination of the mode of action
  • Risk assessment
  • Evaluation of cosmetic ingredients and formulations
  • Customer-specific development of new models and test procedures

Applications

  • Eye Irritation Test
  • Wound healing
  • Transport studies
  • Analysis of cell viability and barrier integrity
  • Morphological and anatomical study of tissue models
 

Press Release / 19.11.2020

Project launch »ImAi«

New test procedure to replace worldwide standard animal testing - project launched

Your local contact

Christian Lotz

Contact Press / Media

Dr. Christian Lotz

Deputy head of in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-82596

Human in vitro blood-brain barrier model

In-vitro-Modelle Blut-Hirn-Schranke
© Fraunhofer ISC

The blood-brain barrier (BBB) is one of the tightest barriers in the human body, protecting the sensitive central nervous system from cytotoxic effects and pathogens.

By aid of human induced pluripotent stem cells (hiPSCs), we are able to offer patient and disease specific in vitro test systems of the BBB to investigate costumer specific issues. Our BBB model can be used as an evaluation tool in preclinical research and development, such as in drug transport or infection studies.

Structure of the in vitro blood-brain barrier models

Transwell models for analytical substance testing

In-vitro Model Blood-Brain Barrier
© Fraunhofer ISC

Services

  • Transport studies to analyze transport kinetics, efflux rate and permeability coefficient of a test substance
  • Analysis of gene/protein expressions
  • Investigation of cell viability and cytotoxicity
  • Measurement of transendothelial electrical resistance (TEER) for barrier integrity analysis
  • Customer-specific development of new models and test procedures

Applications

  • Drug development for diseases of the central nervous system (e.g. epilepsy, Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis)
  • Infection studies with human-specific pathogens (e.g. Neisseria meningitidis)
  • Preclinical studies for drugs, components, formulations or nanoparticles

Your local contact

Antje Appelt-Menzel

Contact Press / Media

Dr. Antje Appelt-Menzel

Project leader in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-80771

  • Send email

Human primary cell-based intestinal models

In-vitro intestinal model
© Fraunhofer ISC
Intestinal model infected with Salmonella Typhimurium: Cell nuclei are shown in cyan, cellular cytoskeleton in magenta and bacteria of the species Salmonella Typhimurium in yellow.

The intestine is the largest internal organ of the human body with multiple functions that arise from the structural and cellular composition of the intestinal epithelium. While the vilus regions of the epithelium predominantly contain differentiated cells with different functions, stem and precursor cells of the epithelium are located in the intestinal crypts.

In vitro, the stem cells of the epithelium can be cultivated as organoids, which are used to construct human Transwell®-like tissue models with a biological extracellular matrix as scaffold. After maturation in vitro, all cell types of the human epithelium with characteristic structural and biological properties can be reproduced in the models.

Depending on the research question, the gastrointestinal models of the Fraunhofer TLC-RT are used in basic research, biocompatibility studies, drug and tox screening, disease modelling or infection studies.

In-vitro-Modelle Gastrointestinaltrakt
© Fraunhofer ISC

Services

  • Testing of novel carrier structures small intestinal tissue engineering
  • Bioavailability studies (transport kinetics, efflux rates and permeability coefficients)
  • Toxicity (cell death, cell viability and proliferation analyses) and characterization studies (ultrastructural and immunohistochemical analysis of cytoarchitecture, gene and protein expression profiling, determination of barrier integrity and functionality)

Applications

  • Matrix development and testing for small intestinal tissue engineering
  • Drug screening in the context of human diseases of the gastrointestinal tract (e.g. Crohn's disease, ulcerative colitis, etc.)
  • Bioavailability studies of customized test substances such as novel nutrient components in food and/or feed
  • Infection studies with human pathogens (e.g. Salmonella Typhimurium, Campylobacter jejuni etc.)

Your local contact

Daniela Zdzieblo

Contact Press / Media

Dr. Daniela Zdzieblo

Project leader in-vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-82164

Skin models as an alternative to animal testings

© K. Dobberke for Fraunhofer ISC

The skin protects the human body from potentially dangerous influences and forms the interface with our environment. It is therefore important to maintain the health and functionality of the skin.

At Fraunhofer TLC-RT, we have therefore developed methods for producing skin models from human skin cells in vitro that can be used to identify harmful substances or to demonstrate a positive influence on the skin. Depending on the question, an epidermal, an epidermaldermal and a vascularized skin model can be used.

In addition, various skin diseases such as malignant melanoma can be simulated in vitro, enabling the development of new therapies in vitro.

Invitro skin models
© Fraunhofer ISC

Services

  • Broad portfolio of established test methods (e.g. anti-inflammatory, barrier function, keratin aggregation, skin irritation)
  • Established wound healing model
  • Customer-specific development of new models and test procedures

Applications

  • Efficacy testing of topical and systemic drug candidates
  • Determination of the mode of action
  • Risk assessment
  • Evaluation of cosmetic ingredients and formulations

Your local contact

Florian Groeber-Becker

Contact Press / Media

Dr. Florian Groeber-Becker

Head of in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Neunerplatz 2
97082 Würzburg, Germany

Phone +49 931 31-86669

  • Send email
Christian Lotz

Contact Press / Media

Dr. Christian Lotz

Deputy head of in vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-82596

Angela Rossi

Contact Press / Media

Dr. Angela Rossi

Head of Industrial Testing

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-88002

Verena Schneider

Contact Press / Media

Verena Schneider

Project leader in-vitro Wound-healing studies

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 4100-136

3D tumor test systems on a biological matrix

In-vitro Tumourmodel
© Fraunhofer ISC

As a unique selling point, the tumour test systems developed here integrate the structure of the basement membrane after decellularisation of a pig intestine for the physiological anchoring of carcinoma cells. These models enable drug testing at different stages of development and analysis of modes of action.


Tumor cells grow in different tissue niches as monolayers or as aggregates also in coculture with fibroblasts, endothelial and/or immune cells. Bioreactors extend the test periods to several weeks and can adapt the culture to more physiological conditions.

Generation of 3D models
© Fraunhofer ISC
Generation of 3D models from pig intestine
In-vitro bioreactor
© Fraunhofer ISC
In vivo adaptation through bioreactors
Endothelial cell barrier
© Fraunhofer ISC
Endothelial barrier tests

Services

  • Generation of 3D models from pig intestines
  • In the 12-well format, tumour tissue is generated within 11 days for subsequent flexible tests from day 1 to 7
  • Promoting the growth of tumour tissue through bioreactors
  • Bioreactors allow drug testing over several weeks

Applications

  • Tests including the endothelial barrier
  • For transmigration studies of immune or tumour cells, endothelial cells can be added on the other side of the matrix
  • Tests including the tumour stroma
  • Immunotherapies such as BiTE and CAR T cells can be tested
 

Project »FORTiTher«

Until 2022 we are participating in the project "FORTiTher" Research Association for Tumor Diagnostics for Individualized Therapy with the following subproject:

Robot-based production and analysis of personalized 3D tumor models for in vitro testing of advanced tumor diseases.

Your local contact

Sarah Nietzer

Contact Press / Media

Dr. Sarah Nietzer

Project leader in-vitro Test Systems

Translational Center Regenerative Therapies TLC-RT
Röntgenring 11
97070 Würzburg, Germany

Phone +49 931 31-82596