Living cells are the main components of nature and human life. Understanding cellular evolution and the interaction with its molecular environment is essential for finding cures for diseases such as cancer and diabetes. For this purpose, living cells must be examined in areas of application such as toxicology, regenerative medicine, environmental monitoring, basic research – if possible without animal experiments. This is exactly what the Munich based company cellasys does. Whatever the research, no animal experiments.
“I studied electrical engineering at the Technical University of Munich and then came to the Chair of Medical Electronics for my diploma thesis, where I had the task of reading out a miniaturized oxygen sensor that was so small that it could be used to measure the oxygen consumption of a composite of biological living cells. This was the basis for cellasys,” says the managing director and co-founder of the company. “We made it work in the thesis. I also spent some time in the industry, but then did my doctoral thesis at the TU.”
This thesis was the birth of the IMOLA (Intelligent Mobile Lab) technology. “At some point, it worked that we had a system with which we could measure the acidification of living cells. This means that protons emitted by living cells were able to measure oxygen consumption and morphological changes, i.e. how strongly cells adhere to a surface. In 2007, we finally founded cellasys as a spin-off of the Technical University of Munich.”
The central field of activity of cellasys is the measurement with microphysiometric systems or the measurement of various parameters in the microenvironment of living cells. These are the extracellular acidification (pH), the cellular respiration (pO2) and the morphology (bioimpedance) of the cells. The measurement is marker-free, parallel, continuous and in real time. Thus, e.g. in medicine, the efficacy of drugs can be determined before the start of therapy on a cell sample outside of humans (or animals). In the field of laboratory technology, for example, it is possible to continuously investigate the vitality of cells in a micro-fermenter.
For about five years, cellasys has been cooperating with the Academy for Animal Welfare in Neubiberg near Munich, where it operates its systems in the cell culture laboratory and can also keep living cells alive in order to conduct research in the field of toxicology, for example.
“We have cells living under sterile conditions, fibroblasts, with which we can do such investigations. In the field of toxicology, these are investigations to find out, for example, eye irritation problems of new cosmetics, shampoos, etc., without having to test it on a rabbit eye. We do this on connective tissue cells,” explains Wiest. “The Academy for Animal Welfare has been researching this for a very long time and is trying to advance alternative methods. You’ve seen that our technology has potential, and that’s why we have these collaborations and are making a variety of applications in toxicology.”
From research to official approval, however, it is a long and rocky road, which Wiest also had to walk. “We’ve already shown that we can replace this rabbit eye irritation test. We went the administrative route and tried to allow the whole thing, but failed at OECD level,” he says, but promises not to give up. “It was a huge effort to get this far, and it is, of course, frustrating that it will not be followed up there. But we’re on it.”
“A human is not just 80 kilograms of rat”
Neubiberg is also working on “repeated dose toxicity”, i.e. long-term toxicity. “Currently, this is done with feeding experiments on rats, but it can also be done with liver cells that are also observed in our system. So there are alternatives to animal testing. cellasys conducts research in this field and presents the results. In addition, animal experiments would be limp anyway and, apart from the ethical concerns, his experiments on living human cells would also be more effective. “There are also scientific concerns that an experiment can be transferred from a rat to a human being,” stresses Wiest. “Within certain limits, that’s true, but of course a human is not just 80 kilograms of rat.”
Cellasys has just been nominated for the Lush Prize for its “skin on a chip” technology. For this purpose skin models or living skin are ordered, which are bred in laboratories in the USA and Slovakia, because “a human skin model is of course much better than if you have e.g. fibroblasts”.
The cells are stored in a heating cabinet heated to 37 degrees Celsius, which corresponds to the human body temperature. “The cells live here and are fed twice a week by us. So we have regularly living cells available, which we can use for our experiments.”
Of course, these cells must be kept under absolutely sterile conditions to avoid any contamination. “Otherwise it’ll get critical.” Therefore, neither eating nor drinking takes place in the laboratory. Everything is prepared in an aseptic, locked work area, into which only gloves may be put before the scientists go to the measuring system.
“The cells grow exponentially. There are about four million cells in one vial, an experiment requires about 300,000 cells. Of these four million, I take 100,000 and put them back into such a vial and in one week it will be another 4 million,” said Wiest describing the course of the cell culture. “A fibroblast cell is round; if it has docked to the surface, it is elongated [see cover photo]. When she is well, she rolls off again, constricts herself, and then the cell division begins. That’s why the cells usually travel in pairs.” [The process of cell division is clearly visible on the cover picture at various stages].
The cells shown on the cover picture are connective tissue cells of a mouse. However, thanks to the German collection of microorganisms and cell cultures, no mouse had to be sacrificed in order to obtain these cells. You can order various cells there. “They’re frozen there and then made available to various labs. It is also possible to order human liver or tumour tissue and other types of cells,” said Wiest. “These cells have been immortalised, which means that these cells can be kept alive in the warming cabinet for months and can then always be removed for experiments.
However, these two-dimensionally growing cells, which adhere to a surface, are not suitable for certain experiments, he emphasises. “They are sufficient for the prediction of eye irritations, but if one wants to reproduce more complex processes in the human body in the model, one needs three-dimensional cell constructs.
These are also bred in the laboratory and can be ordered. More about that in the next part of this series.