Regenerative medicine Research on cellular processes

Cartilage cells under simulated weighlessness

As cartilage  has very poor healing abilities, the treatment of osteoarthritis and other cartilage damage (e.g. as a result of accidents) is lengthy and often does not lead to a complete recovery. A possible treatment method involves removing a piece of cartilage from the patient, cultivating the cartilage cells and then implanting them back into the patient. Unfortunately, the cartilage cells (chondrocytes) undergo an adaption process during cultivation that is also known as dedifferentiation. In dedifferentiation the cells lose the ability to produce high-quality cartilage. Experiments carried out in space and under simulated weightlessness using random positioning machines (RPM) suggest that dedifferentiation is slowed down under such conditions. We are examining whether this hypothesis can be confirmed and what the possible underlying biological mechanisms for such behavior could be.

Mechanosensitive ion channels

Regular mechanical stimulation and movement is essential for human health. Insufficient mechanical exertion can have drastic effects on the human body, as can be observed in astronauts and patients on earth who are confined to bed. Biological cells have various different mechanisms with which they can register mechanical forces. It is still unknown exactly how the cells detect these forces. Previous studies have shown that mechanosensitive ion channels may be partially responsible. These channels open up when under mechanical pressure and allow the flow of ions through the cell membrane. This research examines mechanosensitive ion channels under normal gravity and under weightless conditions. This process shows promise in the search to find indications as to how cells can detect external forces. In order to examine this, a host cell that generates a large quantity of such ion channels is required. The egg cell of the African clawed frog (Xenopus laevis) has been identified here as a suitable host cell. At the competence center, we have developed a system that enables electrophysiological measurements to be made under various gravitational conditions.

Random Positioning Machine

The “Random Positioning Machine” (RPM) is used to expose biological samples to simulated weightlessness. To produce microgravity the samples are in constant motion. The rotational movement is controlled through algorithms so that the gravitational vector is equal in all directions. This averages out the gravitational force that acts on the sample over a long period of time.

Ground Based Facilities

Elektrophysiology

One way that cells can detect external forces is through mechanosensitive ion channels. The ion flow through these channels can be determined with the help of electrophysiological measurements. We carry out this test on egg cells (oocytes) from the African clawed frog, which generate a large quantity of such ion channels. The electrical conductivity of the cell membrane changes depending on the probability that the ion channels will open.

Among other features, the system developed by the competence center includes a special measuring chamber that permits such electrophysiological measurements to be made under different gravitational conditions. The egg cell is positioned in a silicon chip located in a cavity. A small opening on the underside of the cavity isolates a small part of the cell membrane. The conductivity can then be measured on this piece of membrane using four electrodes. As the measured conductivity is not only dependent on the tested ion channels, the background signal also has to be defined. The isolated part of the membrane is in contact with a microfluidic chip, with which three different fluids can be applied to the cell membrane. The ion channels can be specifically blocked through the application of pharmaceutical ingredients, which in turn allows the background signal to be defined. The actual conductivity through the ion channels can then be determined by subtracting the measurement results achieved with the blocker from those without the blocker.

CEMIOS