Where in the lab are mini-organs growing at the MDC? Not in a test tube, but at the bottom of a plastic disc with 48 well plates and a bright pink nutrient solution. The organoids live in a piece of gel on the bottom of each well. They are much more similar to bodily tissue than a conventional cell culture, in which cells grow in a thin layer at the bottom of the culture flask.
There are mini-colon cancers and mini-renal tumors in Professor Walter Birchmeier’s laboratory. His colleague Dr. Annika Fendler slides a culture plate full of organoids under the microscope, looks through it, and sees balloon-like shapes, some of which are half a millimeter in size. “In an amalgamation of several thousand cells, much more natural conditions prevail than in a normal cell culture,” says the cancer researcher.
The tumor organoids consist of cell types that are already specialized. For example, a mini-intestine has an inner and external surface and the cells are organized accordingly. Tumor organoids are similarly heterogeneous in composition to tumors in the human body.
The better model system
All these properties are useful for research. For when it comes to choosing the right cancer drug, the laboratory results should be as meaningful as possible and easily transferable to the human organism.
“One can generate 3D cultures from patient tissue, test many active substances, and then see what the cells are most responsive to – and therefore also what patients are responsive to,” says Annika Fendler. If the medication has already been approved as an anti-cancer drug, this strategy can even replace tests with laboratory animals and enable personalized therapies. In the search for completely new therapeutic agents, this can reduce the number of animals used.
Signaling pathways in tumor stem cells
In her research project, Annika Fendler is working on clear cell renal cell carcinoma. She has sorted cancer cells out of the diseased tissue and produced organoid cultures, thereby identifying those cell populations that have stem cell characteristics. In the body, these tumor stem cells enable the tumor to keep returning and spread to other organs as metastases.
How can these stem cells be stopped? Annika Fendler discovered that in renal cancer stem cells, the biochemical Wnt and Notch signaling pathways are impaired. These pathways are important, as they enable cells to communicate with one another during their development and specialization. When the enzymes involved mutate, this development gets out of control and tumor stem cells are formed. The good news: drugs already exist which inhibit these signaling pathways.
In the laboratory cell culture, the tumor stem cells uncoil their genetically stored development program, enabling the organoids to be formed – both for research and the enjoyment of every observer who drops by Professor Birchmeier’s lab.