Advances put to use by startups

Standardizing cultures using micro-structured hydrogels

The hydrogel cell culture platforms being developed by SUN bioscience, a spin-off from the Laboratory of Stem Cell Bioengineering, aim to standardize the culture of organoids. This will save researchers time by facilitating the practical work and make experiments more reliable and easier to reproduce.

From intestines to livers and hearts, organoids of various types have already been produced in these micro-structured “molds”. “We’ve even managed to grow organoids that are usually difficult to culture, such as the retina,” says Nathalie Brandenberg, who co-founded the firm with Sylke Hoehnel. “When we found that the differentiation rate for retinal cells was 90% with our platform, compared with the 60% rate previously achieved, we realized just how much potential our device has.” The technology developed by this startup, which was created in 2016, is already being using by pharmaceutical companies. “We’ve had very positive feedback,” says Brandenberg.

Their invention is also being used in CHUV studies into diseases such as cystic fibrosis. A micro-intestine produced using adult stem cells could be used to test how patients suffering from this disease react to the latest treatments available on the market.

The importance of the culture environment and ad-hoc nutrients

The extracellular matrix is essential for ensuring that organoids grow properly. The stem cells that create these organoids are currently cultured in an animal-based gel, which can skew the results of experiments in a number of ways. The startup QGel, which is based in EPFL Innovation Park, has developed a synthetic gel that can be adapted to each type of organoid in order to make the experiments more reliable and easier to reproduce, and to scale up the use of organoids.

This gel makes it possible to grow micro-tumors that can be used to test an array of molecules representing potential treatments. In the field of personalized medicine, QGel is also working on growing the tumor cells of individual patients in order to test and identify the most effective drug. In late 2016, this spin-off from the Laboratory of Stem Cell Bioengineering raised 12 million dollars for its development.

Organoids observed like never before

The spin-off Viventis Microscopy has developed a new type of light sheet fluorescence microscope that can create a time lapse of a living organoid. By photographing the organoid every five minutes for five days, it paves the way for an array of new experiments. It is possible, for example, to accurately follow how one stem cell develops into an intestinal organoid. Several samples can even be observed at the same time.

Light sheet fluorescence microscopes, which illuminate just one slice of the sample, are widely used in labs. As the laser beam is focused only in one direction and sheds very little light in the other – thus forming a sheet – it is possible to observe precise layers of a sample. But until now, several samples of living cells could not be observed at the same time. Two life scientists, Petr Strnad and Andrea Boni, who run the startup, tweaked the microscope to make this possible.

Their system can also be used to observe the development of several living samples at different scales (such as zebra fish, a mouse embryo and the C. elegans worm). Several of these microscopes are already being used by labs in Basel and at EPFL.