Early Stage Researcher Ilkka Fagerlund’s job is rather unique: he produces brain organoids – mini brains of a sort – for research into brain diseases
Thanks to a recently developed technique, human stem cells can be programmed to produce three-dimensional structures resembling the human brain. What is more, these structures also have nearly all of the brain cell types present. In his PhD project, Fagerlund aims to introduce microglia cells to brain organoids. Microglia cells are not naturally formed in brain organoids; however, having them there would make brain organoids better suited for Alzheimer’s research, among other things.
Working in the research group of Associate Professor Tarja Malm at the A.I. Virtanen Institute for Molecular Sciences, Fagerlund produces brain organoids from cells of patients diagnosed with Alzheimer’s disease, and their healthy controls.
“This way, disease genes are also included.”
Donated skin cells are reprogrammed into stem cells, which produce clusters with three embryo layers in them. In real life, too, the human brain develops from the outer embryonic layer. This is why the cell clusters are put in a growth solution that promotes the development of the outermost embryo layer, while stopping the development of others.
“Each organoid is embedded in a drop of protein gel that supports the formation of the organoid structure. Furthermore, organoid growth is also supported by keeping them in a spinning motion.”
Due to the absence of blood vessels, a brain organoid can reach a maximum diameter of five millimetres.
“Each organoid is also unique because they are allowed to develop naturally – although I’m not sure if that’s the right choice of words in this context. Cells produce the growth factors guiding their development independently, and interaction between these growth factors affects the outcome.”
For instance, organoids have a varying number of developmental centres, which resemble the brain ventricles. Moreover, dots that react to light will appear on some organoids. This sounds wild, but it is explained by the fact that the brain and eyes share some developmental stages.
Brain organoids do not have any brain immune cells, or microglia cells, because these are not formed in the outermost embryo layer.
“Microglial function is disturbed in Alzheimer’s disease, and this is why it is also important to study them in brain organoids.”
“We have already succeeded in introducing microglia differentiated from stem cells to brain organoids. However, we still need to get their ratio to nerve cells better in line with real human brains.”
Fagerlund believes that brain organoids will find a good deal of use in the future, especially if they can be produced at an increasingly consistent quality.
“Globally, brain organoids have been used to study disturbances in brain development and the effects of the Zika virus, among other things.”
Fagerlund holds a Master’s degree in biotechnology and, before finding himself immersed in brain research, he worked with viruses, wood-decay fungi and industrial enzymes.
“I’ve tried to adopt a diverse set of methodologies. In this work, the most recent methods can be used to study an important topic.”
Training in the use of the methods was offered by Professor Jari Koistinaho’s research group, which also provided the patient cell samples. The group’s research is supported by the Academy of Finland.