Filtern
Volltext vorhanden
- ja (2)
Gehört zur Bibliographie
- ja (2)
Dokumenttyp
Sprache
- Englisch (2) (entfernen)
Schlagworte
- reconstructed human epidermis (2)
- 3D models (1)
- air-liquid interface (1)
- artificial membrane-permeability (1)
- asthmatic bronchial epithelium (1)
- cytotoxicity (1)
- embryonic stem cell (1)
- embryonic stem cells (1)
- epithelial cell culture (1)
- full thickness skin (1)
- human liver cells (1)
- in vitro models (1)
- in-vitro models (1)
- long-term (1)
- metabolic flux analysis (1)
- multicellular tumor spheroids (1)
- necrosis-factor-alpha (1)
- on-a-chip (1)
- organ-on-a-chip (1)
- organotypic (1)
- permeability (1)
- primary human hepatocytes (1)
- pulmonary drug-delivery (1)
- respiratory syncytial virus (1)
- transport studies (1)
- vesicle-based barrier (1)
Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs liver, lung, skin, brain are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.
Models of the outer epithelia of the human body namely the skin, the intestine and the lung have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.