Scientists create 3D-printed brain-like tissue from stem cells – ABC Online


Scientists in Australia have used a 3D printer to create nerve cells found in the brain using a special bio-ink made from stem cells.

The research takes us a step closer to making replacement brain tissue derived from a patient's own skin or blood cells to help treat conditions such as brain injury, Parkinson's disease, epilepsy and schizophrenia.

The bio-ink is made of human induced pluripotent stem cells (iPSC), which have the same power as embryonic stem cells to turn into any cell in the body, and possibly form replacement body tissues and even whole organs.

Jeremy Crook, who led the research, said the ability to customise brain tissue from a person's own body tissue was better for transplantation.

"That circumvents issues of immune rejection, which is common in organ transplantation," said Dr Crook, from the University of Wollongong and ARC Centre of Excellence for Electromaterials Science.

"It's personalised medicine."

Dr Crook said many neuropsychiatric disorders result from an imbalance of key chemicals called neurotransmitters, which are produced by specific nerve cells in the brain.

For example, he said, defective serotonin and GABA-producing nerve cells are implicated in schizophrenia and epilepsy while defective dopamine-producing cells are implicated in Parkinson's disease.

The team used 3D printing to make neurones involved in producing GABA and serotonin, as well as support cells called neuroglia, they reported in the journal Advanced Healthcare Material.

In the future, they plan to print neurones that produce dopamine.

"We might want to make a tissue that specifically generates that neurotransmitter for grafting into the brain of a Parkinson's patient," said Dr Crook.

"That's absolutely achievable."

To make the neurones, Dr Crook and colleagues used their bio-ink to print layers of a hatched pattern to create a 5 millimetre-sized cube.

They then "crosslinked" the cube into a firm jelly-like substance.

Growth factors and nutrients were then fed into the holes of this spongey "scaffold", encouraging the stem cells to grow and turn into neurons and support cells, linking up to form tissue.

Waste was also removed via the holes in the scaffold.

Dr Crook said once scaled up, blood vessels would be needed, but small transplants could be theoretically possible using the tissue developed so far.

Tissue engineer Makoto Nakamura from Toyama University in Japan said the study was "very impressive".

"This article indicates the good feasibility of 3D bioprinting with human iPS cells to engineer neural tissues," said Professor Nakamura, who recently wrote an overview on the use of 3D bioprinting in the journal Tissue Engineering.

But he said there were also risks with the technology.

A close up of the 'scaffold' made of 3D-printed induced pluripotent stem cells (iPSCs)

(Supplied: Gu et al/Advanced Healthcare Materials)

A close up of the 'scaffold' made of 3D-printed induced pluripotent stem cells (iPSCs)

Supplied: Gu et al/Advanced Healthcare Materials

One of the challenges of using iPSCs is that, like embryonic stem cells, they have the potential to develop into teratomas disturbing looking tumours that contain more than one type of tissue type (think toenails growing in brain tissue, or teeth growing in ovary tissue).

According to Professor Nakamura, it would be important to ensure all the stem cells had turned into nerve cells in the final transplanted material.

"Undesired tissue may grow if even only one immature [stem] cell contaminates [the tissue to be transplanted]," he said.

Dr Crook said the team was currently carrying out animal experiments to test if teratomas developed from the 3D printed nerve cells.

While this is a first step towards 3D printing of whole organs, Dr Crook said a whole functioning brain would be a much more complex task.

"That's a whole different scale. The tissue we print is uniform, and not made up of different regions like a brain," said Dr Crook.

Still, it is a goal the researchers are heading towards.

"We would like to get as close as possible to replicating the function of the brain on the bench," said research team member Professor Gordon Wallace.

Apart from providing customised transplants, 3D printed tissue could be useful for medical research.

For example, tissue from a patient with epilepsy or schizophrenia could be created, specifically to study their particular version of the condition.

"You can compare how neuronal networks form differently compared to healthy patient," said Dr Crook.

And the tissue could also be used to screen for effective drugs or electrical stimulation treatments.

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Scientists create 3D-printed brain-like tissue from stem cells - ABC Online

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