Transplanted human neurons (green) & nuclei (purple). Credit: Drs Raquel Real, Antonio Trabalza & Vincenzo De Paola.
Human brain cell transplant offers insights into neurological conditions
11 Oct 2018
Scientists have created a ‘window’ into the brain, which enables researchers to watch in incredible detail how human brain cells develop and connect to each other in real time.
In the new study, MRC funded researchers for the first time successfully transplanted disease-specific human brain cells, created from stem cells, into a mouse brain and watched how they grew and connected to each other. This allowed the team to study the way human brain cells interact in a more natural environment than was previously possible.
The team, led by Imperial College London in collaboration with a group from the University of Cambridge, used the technique to produce a model of Down’s syndrome, using cells donated by two individuals with the condition.
Analysing how brain cells develop and interact with each other is difficult because scientists usually have to work with post-mortem brain tissue. In this study, the scientists were able to produce a living model of the brain, in a complex genetic disorder, which mimicked the development of complex neuronal networks.
The scientists say that using the technique to produce disease-specific, living brain tissue could help researchers study a range of neurological disorders in the future.
The research, published today in Science, describes how the team saw differences in the brain cells from the individuals with Down’s Syndrome compared to brain cells from a person without the condition.
Although some of the connections between the brain cells from the individuals with Down’s Syndrome were more stable and abundant, they communicated in a slightly less coordinated fashion.
Dr Vincenzo De Paola, lead author of the research from Imperial’s Institute of Clinical Sciences, said: “Scientists have been struggling to develop a way of monitoring live human cells and their connections in the brain. This new approach may have taken us one step closer to this.”
Crucially, the technique allows scientists to study how brain cells communicate, explained Dr De Paola: “The connections between brain cells, which enable them to talk to each other, is often the first thing to be damaged in conditions such as dementia and Parkinson’s. This happens long before the brain cells themselves start to die. But the connections are so tiny, that no type of scanning tool we currently use, such as MRI or PET scans, can see them. But the revolutionary microscopy technique used in this study – called in vivo 2-photon microscopy – allows us to not only see individual live brain cells, but also the connections between them.”
In the study, collaborators in Cambridge created human brain cells by reverse-engineering skin cells. This process involved taking a few skin cells from volunteers with Down’s syndrome, and then reprogramming them in the lab to form brain cells. These were then implanted back into the brain of a mouse.
Dr De Paola explained: “The human brain cells not only formed complex networks, but also started communicating very similarly as they would in the brain. We were hoping a few of the human brain cells would grow within the mouse brain – but we were stunned to see the human brain cells thrive, and soon talk and work together. Eventually the human cells constituted a large area in the mouse brain – around the size of a lentil.”
However he cautioned: “It is still not clear to what extent the transplanted human brain cells resemble the organisation and complexity of their counterparts in the human brain. We now need to investigate this with further experiments.”
The team now hope to refine this technique, and potentially use this approach to study other neurological conditions.
This paper is available on Europe PMC.