December Improved blood vessels make better ‘mini-brains’ in the lab

Scientists have discovered a new approach to growing mini-brains in the lab which gives them long enough lifespan to explore function and disease in cells.  

 The research team led by Dr Mihai Lomora, a scientist with CÚRAM - the Research Ireland Centre for Medical Devices based at University of Galway, grew the small blobs of brain cells in a soft, biologically compatible material called a hydrogel and introduced cells that can form blood vessels.  

 The result was that the cerebral organoids grew larger with fewer cells dying in the centre, and they mimicked features of the protective blood-brain barrier, potentially making them more relevant lab models to study diseases such as stroke, Alzheimer’s, and Parkinson’s Disease. 

 The findings have been published in the prestigious journal Advanced Science. 

 Dr Lomora, a lecturer in Biomaterial Chemistry, lead of the CerebroMachines Lab and member of the Institute for Health Discovery & Innovation, University of Galway, said: “Growing ‘mini-brains’ in the lab might sound like science fiction. But it’s not so far-fetched. Scientists around the world today grow small ‘cerebral organoids’ made of brain cells. 

 “When we started the project, we could see in the scientific literature that cerebral organoids growing in the lab tended to have a vasculature or blood vessels that were superficial only. That meant that the blood vessels didn’t penetrate in to reach the deeper cells in the organoid, then these cells became starved of oxygen and nutrients over time and they died off.” 

 The research project involved a multi-disciplinary team based in CÚRAM, University of Galway, RCSI University of Medicine and Health Sciences, Trinity College Dublin and the University of Edinburgh. 

 The team took an approach to help overcome the issue of viability of an organoid – tiny clumps of tissue, only a few millimetres across and just about visible to the naked eye. One of the main problems with these collections of brain cells is that as they get bigger, a lack of blood supply means the inner core dies off. 

 In order to get enough oxygen and nutrients to all of the cells, researchers adapted an existing protocol, or recipe, for growing the cerebral organoids, experimenting with different environments and timings to optimise the ability of blood vessels to reach these deeper cells.  

 The more blood-vessel-friendly approach resulted in three times less cell death in the organoids, and the researchers saw evidence that the organoids contained characteristics of an important protective feature naturally found in the brain called the blood-brain barrier. 

 Dr Lomora added: “We were fascinated to see that the vasculature really was able to protrude towards the interior of the organoids, which actually was quite a big advancement. And we also saw that cells involved in forming some of those blood vessels came from the organoid itself.  It's at the edge of the state of the art for now. 

“Obviously this is not the same as growing a brain in the lab, but it is a mini-model of how parts of the brain work, and we want it to be as physiologically relevant as possible. We believe that by increasing the vasculature we have taken steps to making the organoids more physiologically relevant.” 

 The organoids are now being used by researchers in the CÚRAM network to explore brain function and disease, including stroke. 

 The research paper is available at Advanced Science.  

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