“Mice have brought us a lot in neurological research”, biologist Vivi Heine admits. “But they have an important shortcoming too. In many neurological and psychiatric disorders, there is a strong genetic component. And despite being extremely valuable for our research, mice are genetically still quite different from men. In mouse models we can usually modify only one gene per strain, which is an important limitation to our research.”

Stem cell lab

It was with that shortcoming in mind, that Heine was asked, little over a decade ago, to start a stem cell lab at Amsterdam Neuroscience. “Research with Induced Pluripotent Stem Cells has evolved rapidly since its first discovery in 2006”, Heine explains. “Today we are able to simply take a blood sample and ‘transform it back’ into stem cells that can become any cell we want, when given the right environment. Especially for diseases with a strong genetic component, like many neurological and psychiatric disorders, this is extremely valuable. It means we can take some blood from a patient and create a cell culture with the exact same genetic make-up. This is not only of great importance for research into the pathophysiology of a disease. It also creates the potential opportunity to transplant autologous, so ‘own’ cell material to a patient. Transplanting new cells that produce fresh dopamine for patients with Parkinson’s disease could become an option. The risk of immunological rejection of these cells would be diminished in those cases.”

"Major psychiatric conditions
are highly heterogeneous
and may relate to different
causal mechanisms"

Precision psychiatry

Apart from the enormous value that induced pluripotent stem cells already have in research and potentially will have in transplantation for neurological disorders, Heine works on a third, very promising application with her cell cultures. “Major psychiatric conditions are highly heterogeneous and may relate to different causal mechanisms. For example, different genetic risk profiles underlie schizophrenia. These different causal mechanisms are one of the causes why the development of new medication for these diseases goes as slow as it does. But what if we could create a brain-in-a-dish model for each genetic type of patient? That would give us the opportunity to test various drugs on the different genetic subtypes of a disease in the lab. Only after you would get a ‘match’ between a certain drug and a genetic subtype of a disease, you could actually start administering that drug to the patient. It would create, so to say, a possibility to perform precision medicine in psychiatry!”

Precision psychiatry

Apart from the enormous value that induced pluripotent stem cells already have in research and potentially will have in transplantation for neurological disorders, Heine works on a third, very promising application with her cell cultures. “Major psychiatric conditions are highly heterogeneous and may relate to different causal mechanisms. For example, different genetic risk profiles underlie schizophrenia. These different causal mechanisms are one of the causes why the development of new medication for these diseases goes as slow as it does. But what if we could create a brain-in-a-dish model for each genetic type of patient? That would give us the opportunity to test various drugs on the different genetic subtypes of a disease in the lab. Only after you would get a ‘match’ between a certain drug and a genetic subtype of a disease, you could actually start administering that drug to the patient. It would create, so to say, a possibility to perform precision medicine in psychiatry!” 

Cooperation

Her visions of precision psychiatry are not vague images from a crystal ball, Heine ensures. “I truly believe that in the near future we could have the first practical applications of these cell cultures of individual patients. It will take quite a bit of effort, though”, she adds, “and above all a lot of cooperation with different fields. First of all, we need to work closely with experts in human cellular biology and network behavior, to check if our ‘brains-in-a-dish’ resemble the brains of the actual patients close enough. There is, of course, more to pathophysiology than just the genetic profile of the neuronal cells. And where we envision transplantation of stem cells in the brains of, for example, patients with Parkinson’s disease, we will seek cooperation beyond the field of neuroscience. For example, hematologists too, face the challenges of manufacturing clinical-grade induced pluripotent stem cells.” “Genetic factors are significant in the capacity of resilient responses to stress and trauma and to maintain healthy brain networks”, Heine states. “With the development of induced pluripotent stem cells, we can now study how complex genetic make-ups affect cellular behavior and what pathways we need to tackle, to encourage adaptations and rebuild resilience in patients with neurological diseases.”