Groundbreaking discovery positive news for decrease in use of laboratory animals
Maastricht UMC+ laboratory has succeeded in measuring activity in surgically removed brain tissue for 6 days. This unique model gives a new perspective on developing a brain biopsy-on-a-chip for the purpose of medical scientific research. It may reduce the use of laboratory animals for brain research.
Society is increasingly critical about the usefulness and necessity of using laboratory animals for medical scientific research. In addition, researchers increasingly understand why an animal test has limited predictive value for the outcome of a follow-up study in patients. This recent awareness has accelerated the search for animal-free models. For instance, there are research groups in various parts of the world making mini-organs (also known as organoids) from human stem cells. The human brain is so complex in structure and function that making a mini-brain from human stem cells is still in the early stages of development.
Researchers from the Academisch Centrum voor Epileptologie (Academic Centre for Epileptology) at Maastricht UMC+, TU Eindhoven and Leiden University Medical Center – LUMC have jointly developed a new concept in which brain tissue remains active outside the body. This model consists of 3 layers. The basis is a circuit board (type of chip) with 120 electrodes (contact points). Stem cells were grown on this plate, which grew into a layer of nerve cells through stimulation. The aim is for these nerve cells to make contact with the electrodes so that electrical activity can be measured. Finally, a piece of human brain tissue surgically removed during epilepsy treatment was placed directly on the nerve cell layer. The idea was that the nerve cell layer between the brain tissue and the electrodes would act as a biological link and could transmit activity in the brain tissue to the electrodes. This brain biopsy-on-a-chip model was kept in culture and showed epileptiform activity after 6 days.
Maastricht brain researcher Dr Govert Hoogland sees great potential: "New experiments will have to show whether this is a useful model but our approach potentially provides a clinically relevant alternative for non-animal brain research of epilepsy, for example. It opens the way to evaluate new, personalised treatments."
For this research, ZonMw* awarded an Off Road grant to Jean-Philippe Frimat. The Off Road programme gives space to young researchers for pioneering, unconventional research. The research involves (bio)medical and/or health sciences as research area(s) and the aim is to challenge young (bio)medical and health researchers to achieve new insights and unexpected breakthroughs in medical and/or health research.
Dr J.P. Frimat and Dr R. Luttge, Neuro-Nanoscale Engineering (Neuro-Nanoscale Engineering) research group, Microsystems division (TU/e), developed the idea and culture materials. Dr J.P. Frimat is currently working in the Humane Genetica en Neurologie (Department of Human Genetics and Neurology) at LUMC.
Dr O. Schijns, Dr J. Dings, Dr K. Rijkers and Dr G. Hoogland, Neurochirurgie (Neurosurgery) department and School for Mental Health and Neuroscience at MUMC+ applied the idea and culture materials in human brain tissue. PhD student M. Hu and Prof A. van Maagdenberg, Department of Human Genetics and Neurology at LUMC analysed the measured activity.
The research article Spontaneous Epileptic Recordings from hiPSC-Derived Cortical Neurons Cultured with a Human Epileptic Brain Biopsy on a Multi Electrode Array was recently published in Applied Sciences, an international, peer-reviewed, open access journal on all aspects of applied natural sciences published semi-monthly online by MDPI (Multidisciplinary Digital Publishing Institute).
* ZorgOnderzoek Nederland – ZON (Care Research Netherlands) was established by law in 1998 (ZON Act). Since 2001, there has been a partnership between ZON and the Medische Wetenschappen – MW (Medical Sciences) domain of the Nederlandse organisatie voor Wetenschappelijk Onderzoek – WO (Dutch Research Council). This partnership is called ZonMw and constitutes an independent self-governing organisation.