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Tissue engineering: Strengthening industry competitiveness while reducing animal testing

The goal of tissue engineering is to recreate the whole or part of human tissues in vitro. Ideally, the in vitro tissue should fully mimic the morphology and functions of the corresponding native tissue. The industry of tissue engineering is still in its infancy and many of the tissue-engineered products are still at development stages. But it is now a fast growing industry: The potential market of this technology is so huge that revenues may exceed $10 billion by 2013. [1]

The engineered products have two main applications:

1. Therapeutic use - to restore, maintain or improve tissue function, thus offering patients the chance to regain a normally functioning body and

2. For R&D - as tools for developing drugs and chemicals.

With the advent of the human embryonic stem cells, the therapeutic use of engineered in vitro tissues will become increasingly important in the near future. However, in this short article, we will focus on the second application of the tissues engineered in vitro, its use in compound development.

In vitro tissues in compound development

In vitro tissues have several advantages over the animal experiments

- From the physiological and toxicological point of view, the human in vitro tissues are more relevant than animal tests.

- In vitro human tissues are ideal for mechanistic study of chemical’s effect.

- It is possible to carry out high-throughput screening and testing.

- It is more cost effective than animal tests and morally and ethically more acceptable to the public opinions.

Indeed, the animal tests are facing increasing protests from animal activists. The legislation is also becoming more and more stringent: the European Union has decided that as of year 2013 animal tests will be banned for testing cosmetic products [2]. Fortunately, technology for in vitro reconstitution of the human skin equivalent is now mature enough to replace animals for testing cosmetic products. Several companies have engaged in skin business, such as Skinethics, Episkin, MatTek, Phenion, Cell Systems, Straticell, etc. with annual sales higher than 10 million Euros.

For new drug development, the pharmaceutical industry is also interested in tissue engineering. With the development of the high throughput platform, and the creation of chemical libraries, in vitro tissues are becoming a central part of the drug discovery machinery: a relevant cellular and tissue model is the pre-requisite for selecting drug leads. Depending on the nature of the disease or of the drug target, all kinds of in vitro tissues or cells can be used. Keratinocytes, hepatocytes, smooth muscle cells, and neuronal cells, pulmonary cells, etc... The more we understand the underlying molecular mechanisms of a disease, better could we design an in vitro screening model.

The chemical industry is also interested in tissue engineering now, because of the new European legislation on chemicals, REACH (Registration, Evaluation, and Authorization of the CHemicals) [3]. A chemical has to be tested prior to its introduction into the market. It is now the responsibility of the manufacturer to test and evaluate the potential hazards of chemical product. There are more than 30’000 chemical compounds to be tested within the next 11 years. According to the REACH working group, the cost for testing these compounds amounts to more than 3 billion Euros. Clearly, the use of the in vitro engineered tissues is more relevant and cost-effective than the animal tests.

However, in vitro tissues have also their draw-backs: for example, it is not possible to test the systemic effects of the chemicals. Most of the in vitro tissues are devoid of detoxification systems such as the one that exists in liver. Nevertheless, by choosing the relevant tissues for specific purposes, we can overcome these shortcomings. For example, one can use the reconstructed human epidermis for skin corrosion assessment, the reconstructed human airway epithelium for inhalation toxicity, etc.

In vitro tissues on the market

With the combined efforts of different shareholders, the European Union (ECVAM), industrial Partners and scientists, several in vitro tissues have been validated for toxicity tests [4]. There are much more in the process of validation. Validation of an in vitro tissue/model for testing chemicals is necessary for legal purposes (for registration of a chemical by a manufacturer).

Here is a list of the commercially available tissues:

- Reconstructed Human Epidermis (from Skinethics, Episkin, MatTek, Phenion, Advanced Cellsystems, Straticell)

- Reconstructed Human Corneal Epithelium (from Skinethics, MatTek)

- Reconstructed Human mucosa: Oral, Gingival, Vaginal Epithelia (from Skinethics, MatTek)

- Reconstructed Human Airway Epithelium (from MatTek, Epithelix)

Conclusion

Due to the obvious advantages mentioned previously, the use of the human tissues engineered in vitro could greatly enhance the competitiveness of the industry in a global market: it is not only more cost effective, but also more morally and ethically acceptable than animal tests. In view of all these aspects, it is clear that reconstituted human tissues have a bright future and global market will grow exponentially.

About Epithelix

Founded in 2006, Epithelix Sàrl (www.epithelix.com) is a Swiss Biotech company with the aim to develop innovative in vitro solution in the field of respiratory disease and chemical testing. The company develops, produces and sells reconstituted in vitro human tissues. Epithelix also offers high-throughput screening services and testing of chemicals, based on its unique in vitro cell models to research laboratories and chemical, cosmetic and pharmaceutical industries. In most of the cases, reconstituted tissue suffers from their short shelf life (around two weeks). However, the premium technology developed by Epithelix allows the maintaining of reconstituted human tissues up to one year. Indeed this innovative technique gave birth to MucilAir, the first in vitro cell model of the human airway epithelium with a long shelf life. The use of MucilAir enables the first long term testing of compounds and offers economical alternative to animal testing.

Bibliography

[1] ESTO report on Human Tissue Engineering, 2003

[2] Choice, April 2006, 34-37

[3] http://www.reachlegislation.com

[4] http://ecvam.jrc.it