November 1, 2010 (Vol. 30, No. 19)

Epithelix Develops Artificial Tissues that Model the Lining of the Airway and Lungs

While a graduate student at the University of Geneva, Switzerland, Ludovic Wiszniewski, Ph.D., teamed up with three colleagues to optimize a technology platform discovered there. In March 2006, they launched Epithelix Sarl, a company that specializes in tissue engineering. Epithelix develops, produces, and sells reconstituted in vitro human airway tissues for toxicity testing of chemicals and the study of human diseases. Its products also help to reduce the need for expensive animal testing.

Other companies are developing substitutes for animal toxicity tests based largely on liver cells. Epithelix, instead, is developing artificial tissues that model the lining of the airways and lungs. “Our initial focus was on airway tissues because we have special expertise in reconstituting these kinds of tissues,” says Samuel Constant, Ph.D., COO. “Back then, a good in vitro model for airways didn’t exist.”

Epithelix’ core product is MucilAir, a 3-D model of the human airway epithelium made up of primary human cells isolated from the nasal cavity, trachea, and bronchus. Once differentiated, MucilAir mimics the morphology and function of the native human airway epithelia, including beating cilia, active ion transport, and tight junctions. Each culture contains three principal primary cell types—basal, goblets, and ciliated cells. The mucocilliary clearance is fully functional.

“These tissue cultures are as close as possible to the in vivo situation, and they contain no transformed cells,” Dr. Constant says. What’s more, the tissue remains fully differentiated and functional for more than a year.

MucilAir is available in 24-well plates for early screening. Epithelix also sells chemically defined culture media for growing MucilAir and other tissue cultures. “The culture media is the best way to grow tissues and it’s important for a long shelf life,” adds Dr. Constant. All tissue cultures are performance-assayed and test negative for HIV-1, mycoplasma, hepatitis B, hepatitis C, bacteria, yeast, and fungi.

Since MucilAir has a similar microanatomy to that of natural respiratory tract tissue, it responds in the same way to various chemicals. Its ability to stay active for up to one year makes MucilAir ideal for long-term toxicity testing of environmental chemicals, including airborne toxicants, nanoparticles, and ingredients in perfumes, cosmetics, and household products. The company’s technology is the only one that can monitor the chronic effects of environmental toxicants or drug candidates, according to Dr. Constant. Many toxicants, such as components in cigarettes, do not produce immediate tissue damage but require repetitive doses to inflict injury.

Another application for the airway tissue cultures is to evaluate the performance of drugs or drug candidates designed to treat specific respiratory diseases such as asthma, COPD, and cystic fibrosis. Different products created by Epithelix consist of tissues derived from primary human cells obtained from healthy people, smokers, and patients with asthma, allergies, COPD, and cystic fibrosis.

MucilAir™ is sold in a 6.5 mm diameter Corning Transwell with a pore size of 0.4 µm. Each reconstituted epithelium contains about 400,000 cells.

Portfolio Developments

In addition to MucilAir, Epithelix sells primary human cells isolated from nasal (hAECN) and bronchial (hAECB) biopsies and pulmonary fibroblasts. The hAECN and hAECB products are commonly used for in vitro studies related to pulmonary diseases and chemical testing. They are standard for research on asthma, COPD, cancer, cystic fibrosis, and bacterial and viral infections, Dr. Constant notes, adding that they are particularly useful for screening, testing, and validating drug candidates. Epithelix’ tissue-engineering technology platform transfers to other types of tissues, and the next generation of products in the pipeline will be liver and skin tissue cultures.

“The beauty of our technology is that we can ship ready-to-use tissue worldwide. Scientists can use our tissue as soon as it is received, and there’s no need to culture it.”  

“The key message,” says Dr. Constant, “is that we have to think about the long-term effects of chemicals.” The current in vitro systems expose cells to chemicals and give only short-term results. However, many chemicals have long-term effects, and repeated exposures must be analyzed. “Now we have a tool to do long-term testing.”

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