Modern cell biology would be inconceivable without cell cultures. Several thousand cell lines from humans and from more than 150 animal species are cultivated outside the original organisms under controlled conditions in laboratories around the world. However, growing cells on the flat surfaces of tissue culture plates has the major drawback that cells do not behave as they would in their natural environment. This is why scientists are now using three-dimensional substrates to replicate the natural environmental of cells in tissue (cellular matrix). Dr. Brigitte Angres and Dr. Helmut Wurst, founders and managing directors of Cellendes GmbH in Reutlingen, have taken advantage of this new knowledge and developed two novel hydrogels for cell cultivation.
Cellendes placed a PVA hydrogel on the market in March 2010 and the commercialisation of dextran hydrogels followed in April 2011. Angres: “Research institutes and pharmaceutical companies depend on materials that produce reliable test results. When we looked more closely at the biomaterials and gels that were on market at the time we were considering setting up Cellendes, we quickly found that there was no gel available to enable researchers to set up specific culture conditions. We saw a huge market potential for gels that mimic the characteristics of natural extracellular matrices in all areas where cells are used for analytical and therapeutic purposes, which includes basic research, drug development and medical technology.”
The advantage of Cellendes’ hydrogels over other gels is that the cell environment can be modified to mimic the characteristics of natural extracellular matrices. The behaviour of the cells is therefore very similar to that of the cells’ natural environment, thereby providing researchers with more authentic results. Drug candidates can therefore be reliably selected in the early stages of drug development, before costly animal experiments and clinical trials are undertaken to test the efficacy of the drug under development.
Conventional gels used for the three-dimensional cultivation of cells are mostly produced from animal substrates such as collagen. However, the disadvantage of such substrates is that their composition cannot be altered and potentially unwanted components might be present, resulting in the presence of undefined contaminations and distortion of test results.
The company’s hydrogels are extremely simple to set up. The hydrogel system comes with two liquids, a polymer and a crosslinker, which result in the formation of a gel when mixed. Bioactive factors, e.g. adhesion peptides or extracellular matrix proteins, can be bound to the polymers before the addition of the crosslinker. It only takes a few minutes to prepare the hydrogel. The hydrogels are fully transparent and the cells can be labelled with fluorophores or other suitable markers and easily examined under microscopes, including phase contrast and fluorescence microscopes.
“The 3D hydrogel system, which consists of synthetic and chemically defined components, is designed to give full control over the composition of bioactive components in the gel as well as enabling researchers to test the effect certain substances have on the cells in a three-dimensional environment,” Angres explains. “In addition, the preparation of the gel is relatively simple; no specific experience or equipment is required. These aspects were of crucial importance for us.”
Dextran hydrogels can be degraded by addition of the enzyme dextranase to isolate cells from the hydrogel for further use. The cells can then be analysed biochemically and cultivated differently, if required. “We are the first to offer such a flexible system, a system that is of equal importance for basic research in the field of cell biology and pharmaceutical industry or regenerative medicine applications,” said Angres. On the one hand, users can adapt the systems to the specific culture conditions of their cells and on the other, they can specifically modify the hydrogels in order to study potential effects of the environment on the cells.
The market now needs to be made aware of the hydrogels and their benefits. The company has therefore established an international distribution network to sell the hydrogels worldwide and it also provides marketing support from its headquarters in Reutlingen.
Angres and Wurst, who worked for many years in the product development department of the Californian biotech company Clontech and still hold positions at the NMI Natural and Medical Sciences Institute at the University of Tübingen, had been thinking for a long time about establishing their own business. Cellendes GmbH was eventually founded in 2009 as a spin-off company from the NMI. However, the go-ahead proper came in 2010 when a strategic investor joined the company. In addition, Cellendes was funded under the EXIST research transfer programme from 2010 to the end of March 2012. The NMI provides an ideal environment for start-up companies. “The NMI is an excellent springboard to found a company,” explains Dr. Angres, who is also very impressed by the support provided by BioRegio STERN Management GmbH: “The network, coaching and consulting services available in the Stuttgart area makes company founders feel really welcome.”
Cellendes looks to the future with optimism. A new hydrogel will be placed on the market as early as 2014. Due to its slower gelation time, the advantage of the new gel is that it can be put in special culture vessels (e.g. microchannels) or injected into animals. These research activities are funded under the German Federal Ministry of Economics and Technology’s ZIM-SOLO funding programme. Cellendes is also developing a hydrogel that promotes the formation of blood vessels in implants in an international project that is funded under the German Ministry of Education and Research’s (BMBF) EuroTransBio programme. The project also involves the company ProTip in Strasbourg, the NMI and NMI TT GmbH in Reutlingen.Another project is specifically focussed on bioactive implants. It is funded by the German Federal Ministry of Education and Research (BMBF) and carried out by Cellendes in cooperation with Aesculap AG, TETEC AG and the NMI.Cellendes also works with academic research groups in Baden-Württemberg, which provides the company with further development possibilities: for example, Cellendes is working with Prof. Dr. Margaret Müller’s group in the Medical and Life Sciences Faculty of Furtwangen University (Villingen-Schwenningen campus) and Prof. Dr. Dieter Stoll from the Albstadt-Sigmaringen University of Applied Sciences and the NMI. This cooperative research project is focussed on the development of a standardised 3D in vitro tumour stroma model for testing tumour therapeutics.
Dr. Brigitte AngresCellendes GmbHMarkwiesenstr. 5572770 ReutlingenTel.: +49 7121 15940 11Fax: +49 7121 15940 91E-mail: angres(at)cellendes.com