Lab rat brain created

C&I Issue 9, 2014

Scientists have created a 3D tissue similar to the rat brain. The tissue could offer a better way of studying normal brain function as well as injury and disease, say bioengineers at Tufts University, Boston, US. It can remain living in the lab for more than two months.

‘We show in the paper that you can already use [this model] for screening drugs and we used it to screen the effects of mechanical damage to the brain, like traumatic brain injury,’ says senior author David Kaplan, director at the Tissue Engineering Resource Center at Tufts.

The scientists created a novel donut-shaped structure of two biomaterials, showing the grey-white matter separation of nerve cells or neurons (PNAS, doi/10.1073/pnas.1324214111). Neuronal cultures were placed in a stiff silk protein-based biomaterial; rat neurons placed in this scaffold formed networks and sent projections (nerve axons) through the centre of a soft, collagen-based gel at the centre to neurons on the opposite side of the donut.

‘We used silkworm silk because it is tunable and degrades very slowly and is compatible with cells,’ Kaplan explains, while collagen is good for supporting cell functions. Neurons in the tissue expressed genes involved in neuron growth and function and also showed electrical activity and responses that mimicked signals seen in the intact

‘Work with human-derived cells is now under way and we want to reach our goal of six months in vitro cultivation,’ says Kaplan.  ‘Also, we want to add other human cells to add complexity and make it more relevant to study the human condition.’

‘The ability to grow 3D neural cultures for months is extremely novel. This may be due to the scaffolds used and optimisation of cell density within the cultures,’ says Michelle C. LaPlaca, biomedical engineer at Georgia Tech, US. ‘The authors have tuned the matrices such that stiffer substrate supports the cell bodies and softer substrates allow for axonal growth, beyond the normal in vitro lengths. This is a very interesting approach.’

Meanwhile, neuro-engineer Ulrich Hofmann at University Hospital Freiburg, Germany, says labeling the model as having brain-like properties is an exaggeration, as it shows just live neurons and elasticity.

‘They are promising a Ferrari but they drive by in a VW Beetle,’ he quips. ‘On the other side, the long-term viability of the neurons growing there is a great achievement and is really cool, because growing neurons in 2D is quite difficult for long periods of time.’

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