Alex: We should talk more often. It is very interesting to learn about the science and potential implications for new therapies. I am excited to learn about the transformation of my stem cells into nerve cells. Tell me, what are neural stem cells?
Birgitt: Neural stem cells are the precursor cells of the brain. They can differentiate into multiple cell types such as nerve cells and cells that support neurons which are called glia cells. They are the stem cells of the central nervous system. Even in the adult brain, we can find neural stem cells. Recent studies have shown that physical exercise helps with the regeneration of neural stem cells. So, keep moving!
Alex: I am running and keep moving, that's my motto. It helps a lot with my Parkinson's. What is the concept behind the transformation into neural stem cells?
Birgitt: To understand cell differentiation one must understand the concept of the three germ layer. A germ layer is a group of cells that interacts with one another to create organs and tissues. Humans have three germ layers: the inner layer (endoderm), the middle layer (mesoderm), and the outer layer (ectoderm). Each one of these layers is responsible for creating different tissues of the human body. Nerve cells are derived from the outer layer. In the culture of your induced pluripotent stem cells, we promote the preferential growth of the outer layer cells and suppress the mesoderm and endoderm layers using specific small molecules and proteins in the cell culture media.
Alex: Fascinating, there is indeed more than meets the eye in this process.
Birgitt: Well, the process to transform stem cell into neurons or neural precursor cells has been a tedious and lengthy procedure in the past. However, newer protocols allow us to circumvent several difficulties, and has made the transformation much faster. One procedure in particular has made it possible for pluripotent stem cells to be turned into neural stem cells in only seven to ten days. You can see your stem cells at day 2 and day 6 during the neural induction in the next two images.
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| Alex's stem cells at day 2 of neural induction |
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| Alex's stem cells at day 6 of neural induction |
Alex: Interesting. On the next two images below, my cells look completely different and I can see individual cells, almost like my skin cells.
Birgitt: Exactly, after seven days and one enzymatic treatment to divide the cells, the cells grow in a single layer. They look similar to skin cells, but have a rounder body and a few small processes. The images below are in two different magnifications, the first one is an overview and then a close-up. Looking good!
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| Alex's neural stem cells have formed |
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| Alex's neural stem cells at higher magnification |
Alex: And after that? These are not the dopaminergic neurons that are dying in my brain. I assume there is another step or steps?
Birgitt: Right on, the neural stem cells can be further differentiated into different types of neurons or glia through several different processes. Many research labs develop protocols to make all kinds of different cells of the brain, such as cortical neurons, inhibitory GABAergic neurons, dopaminergic neurons, Purkinje cells, and motor neurons as well as glia cells like astrocytes or oligodendrocytes. The methods for differentiating all these types of neurons can require extended periods of time (up to several months).
Alex: How long does it take to make dopaminergic neurons?
Birgitt: It takes about 4-8 weeks to have fully mature dopaminergic neurons. A long way to go and it needs passion, endurance, and commitment, just as running a marathon. Will talk about them in the next blogs.
Alex: Thanks so much, as always, fascinating and it gives me hope that this research will -some day, hopefully soon- change the lives of people with Parkinson's disease.
