Summary
Organoids are three-dimensional lab-grown tissues made from stem cells that contain the most important cell types of specific organs. There are many types of organoids that model different organs, such as the brain, liver or intestine. Our aim is to use cerebellar and cerebral organoids to recreate PCH2 under laboratory conditions. With a suitable model of PCH2, we can then find out whether and in what way cells with PCH2 differ from healthy cells. Since the cerebellum and eventually also the cerebrum are severely affected, we are currently focusing on these areas. Our hope is to understand how brain development and the functionality of nerve cells differ in brains with PCH2.
Background Information
In order to understand which cellular processes lead to diseases, researchers usually rely on a so-called disease model. This can be an animal model (e.g. a mouse or fruit fly) or, more recently, a model from human tissue that is artificially grown in the laboratory. For this purpose, human stem cells are taken from healthy people or people with diseases and used to grow tissue following a special protocol (a kind of recipe). Depending on the “ingredients”, different tissues can be obtained, which are called organoids. They are three-dimensional and contain the most important cell types of an organ, such as different types of nerve cells in brain organoids. This technique is fairly recent, but offers many research opportunities, especially for diseases that only occur in humans and are therefore difficult to study using animal models.
Brain organoids are used in research to study developmental disorders and degenerative diseases of the brain. They are also used to test potential active substances for various diseases and have become increasingly important in basic and pharmaceutical research.
What Does the Research Project Involve?
Using skin cells from three children with PCH2, we have grown stem cells and are using those to create brain organoids. We are currently investigating how these PCH organoids differ from organoids grown from healthy cells. There are several levels at which we are investigating these differences.
- Firstly, we measure the size of the organoids and find that PCH organoids are smaller than the control group.
- Next, we examine the composition of the cells in the organoids; i.e. the number and arrangement of different cell types. Here too, we see differences.
- The last level that we examine more closely are processes occurring within the individual cell types. This indicates which cellular processes are affected by PCH2.
Together, the three levels of research help us understand how PCH2 develops.
Outlook
Once we have understood which cell types are most susceptible to PCH2 and which processes are affected in these cells, we can start testing active substances on our organoid models with the aim of improving or completely restoring these processes to normal. These findings can then lead to possible treatment options for PCH2.
Conclusion
In order to find an effective therapy for PCH2, we must first find answers to some fundamental questions. Stem cells and organoids can be of great help towards this goal. Similar models are already being used successfully in pharmaceutical research and drug development.
