Cells in the Laboratory: The Right Tool Leads to Success

It all begins with the cell – even in medicine. Biochemists and pharmacologists research new active ingredients, while physicians study specific cell properties and want to make use of the natural potential of stem cells. Cells and cell cultures are being tested in the laboratory to determine everything which could be technically suitable for healing purposes before it comes in contact with the living organism.


Photo: cell

© panthermedia.net/nobeastsofierce

Science has already known what a cell is since the end of the 17th century – at that time, the first plant cells, bacteria and protozoa were discovered and described. Today, cells are the subject of fundamental medical research, but they are not without problems. They are not just too small to be seen directly; their manipulation is also difficult and can distort research results.

Grabbed by tweezers

Science wants to literally “get a grip“ on a cell by using modern technology. To do this, the Fraunhofer Institute for Production Technology (Fraunhofer IPT) developed a hybrid device that is able to achieve non-contact illustration and can hold the cell in place. “We combine a digital holographic microscope with optical tweezers,“ reveals IPT group leader Stephan Stürwald. The previous method of studying the effects of substances on cells provides the background for the device’s origin. The cells are subjected to potential pharmaceuticals in microfluidic chips. In doing so, every single cell needs to be analyzed in its own well, so cells do not interact. It is enormously difficult to transfer single cells into the wells. Until now, they were poured in along with their nutrient solution. Doing it this way however, does not guarantee that there is only one cell in each of the wells. It could just as well be multiple cells or they could be flushed out again.
This is where the optical tweezers come into play, which are actually a laser beam: the pressure of the laser holds or transports the cell. The researchers at the Fraunhofer IPT are therefore not only able to separate cells from each other, they are also able to position them and arrange them in patterns to study their interactions. The digital holographic microscope in turn makes it possible to look at the cells. It shows them as computer-generated holograms without having to use cell markers and dye.
Photo: nanoparticles

Magnetic nanoparticles with a coating of proteins are able to affix themselves to cancer cells. The make precise filtering of cells from the blood possible; © panther-
media.net/Wolfgang Rieger

Removed with magnets

Researchers in clinical diagnostics do not use an optical, but mechanical way to track cancer cells. “Liquid Biopsy“ is an approach with which cancer cells can be filtered from the blood. This process involves long molecular chains that are matched to the surface of the sought after cells, as Dr. Gunther Gastrock from the Institute for Bioprocessing and Analytical Measurement Techniques (IBA) in Heilbad Heiligenstadt explains:”You can basically bind all cells with specific binding sites on their surface to the respective antibody and thus make a selection.“ The IBA developed a cell separator prototype, in which iron oxide nanoparticles bind to cancer cells with a protein coating. A magnet extracts the cell type in question on the nanoparticles from the blood stream, so it can now be analyzed.

Microfluidic chips for liquid biopsy very reliably retrieve cancer cells from the blood even with a low cell concentration. “Circulating tumor cells will play a significant role in the early diagnosis of cancer and to help us understand if treatments are working in our cancer patients by serving as a liquid biopsy to assess treatment responses in real time,“ says Dr. Diane Simeone, Director of the Translational Oncology Program at the University of Michigan Cancer Center. The Center is developing a chip that does not just capture cancer cells, but also cultivates them for further analysis. The device could be ready for use in medical facilities in three years.
Photo: petri dishes

Cells behave differently in Petri dishes than in the human body. To produce outcomes that are more reliable, researchers can try to recreate their natural environment in the laboratory; © panthermedia.net/Sven Hoppe

No more boring Petri dishes

In order to obtain usable results, it is not always enough to be able to observe cells. Research also needs to provide the proper environment for them. Cells “behave“ differently in the laboratory than they do in their natural setting. In the lab, they are kept in a culture medium and stick flatly to the bottom of Petri dishes and microscope slides; in the body however, they form three-dimensional structures with neighboring cells and living, where they interact with each other. In the future, new materials are also meant to offer cells in the laboratory an environment that is similar to the one in the body.

The Karlsruhe Institute for Technology (KIT) presents one possible way: hematopoietic stem cells, which are used to treat diseases like leukemia, have been successfully proliferated here. In the treatment process, patients receive healthy stem cells from a matching donor. Sometimes however, there might not be enough transplants available. So far, the proliferation of stem cells to resolve this issue is not possible, because the cells do not proliferate outside of their so-called microniches in the bone marrow and they lose their specific hematopoietic repopulating abilities. The microniche is an area in the bone where stem cells interact with other types of cells, where they get oxygen and nutrients and whose porous structure gives them support.

In cooperation with the Max Planck Institute for Intelligent Systems in Stuttgart and the University of Tübingen, the researchers at the KIT surrounding Dr. Cornelia Lee-Thedieck have recreated the microniche. With the help of synthetic polymers, they created a porous structure that resembles the hematopoietic bone marrow and supplemented it with proteins to which stem cells can adhere. Finally, they populated the structure with stem cells and their natural neighboring cells. After several days of incubation, the researchers were able to prove that the stem cells proliferated and also partly maintained their hematopoietic repopulating abilities. This accomplished the test objective.

These and similar ideas, for instance the embedding of cells in hydrogels, micro- and nanostructures, show what laboratory techniques and technologies can look like in meaningful research on and with cells. What is more, they prove that you just have to tackle cells the right way to be successful.
Photo: Timo Roth; Copyright: B. Frommann

© B. Frommann

Timo Roth