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Sep 1, 2015 | By Alec

As regular readers will have noticed, 3D printing is already becoming a huge hit in hospitals throughout the world for its ability to produce accurate surgery replicas that help doctors prepare properly. However, the real revolution must surely be in the bioprinting of transplantable tissues, a field in which a team of San Francisco scientists have just shared a breakthrough technique to 3D print tiny models of human tissue for use in drug screening, cancer research and eventually even complete transplantable organs.

This new technique is called DNA Programmed Assembly of Cells (DPAC) and is completely explained in the latest edition of the journal Nature Methods. The study itself took place at the University of California San Francisco – a leading institute in the field of biomedical research – and was led by Zev Gartner, associate professor of pharmaceutical chemistry. It also involved postdoctoral fellow Alex Hughes, PhD, staff researcher Maxwell Coyle, and a number of PhD students.

As they explained, their technique essentially revolves around the creation of the biological equivalent of LEGO bricks – tiny models of human tissues that form the building blocks of the human body. Each is 3D printed into a dish and can be used for a wide range of studies; think about the study of tissue affected by cancer, or for therapeutic drug screening in patients. Eventually, it could even lead to the breakthrough in 3D printed human organs.

In step 1, cells attach to strand A. In step 2, cells attach to strand B. In step 3, cells assemble onto the cells from step 1.

Professor Gartner was very optimistic about the breakthrough, and as he said on his university’s website, there is little that cannot be done with these organoids. ‘We can take any cell type we want and program just where it goes. We can precisely control who’s talking to whom and who’s touching whom at the earliest stages. The cells then follow these initially programmed spatial cues to interact, move around, and develop into tissues over time,’ Gartner says. ‘One potential application would be that within the next couple of years, we could be taking samples of different components of a cancer patient’s mammary gland and building a model of their tissue to use as a personalized drug screening platform. Another is to use the rules of tissue growth we learn with these models to one day grow complete organs.’

What’s more, its very effective. The technique can be used to create arrays of thousands of organoids – each custom designed and containing a few hundred cells each – within a matter of hours. And as our bodies contain more than 10 trillion cells of hundreds of different kinds, these pockets of different cells are absolutely necessary for the structural functions of different organ systems. But cancer tends to break down the organized cell structures, so we need to arm ourselves against it. ‘Cells aren’t lonely little automatons,’ Gartner says. ‘They communicate through networks to make group decisions. As in any complex organization, you really need to get the group’s structure right to be successful, as many failed corporations have discovered. In the context of human tissues, when organization fails, it sets the stage for cancer.’

This makes the DNA Programmed Assembly of Cells very potent, as more knowledge about how tissue cells organize themselves and function helps us further our understanding of how to cure cancer. ‘This technique lets us produce simple components of tissue in a dish that we can easily study and manipulate,” one of the PhD students involved in the study, Michael Todhunter, said. ‘It lets us ask questions about complex human tissues without needing to do experiments on humans.’

And to 3D print the specific necessary structures, Gartner’s team relies on DNA. Essentially, they cut out tiny parts of DNA and engineer it onto the outer membranes of the cell – they compared it the hairs on a tennis ball. Not only does this enable cells to understand where they belong within the organoid, it also ‘glues’ them together. But the beauty is that if the DNA sequences don’t happen to match, they don’t attach themselves to each other either. This enables the creation of very precise cell pockets. The 3D printing of these cellular structures happens in layers, with each set being designed to stick to specific partners of cells.

And to demonstrate the technique’s effectiveness to 3D print different organoids, they 3D printed arrays as diverse as brancing vasculature cells, cells from mammary glands, as well as mammary epithelial cells. In the latter experiment, they added cells with low levels of the cancer gene RasG12V and found that more than one of these mutant cells is enough to kickstart the abnormal growth of cell structures.

So what’s next? Gartner’s team is currently working on plans to use this technique to investigate what changes at a cellular level lead to tumorgrowth and cancers that invade other parts of the body and become life-threatening. They also hope to use this breakthourgh to learn more about building functional tissues that can be transplanted, even up to complete organs. ‘Building functional models of the complex cellular networks such as those found in the brain is probably one of the highest challenges you could aspire to,’ Todhunter says. ‘DPAC now makes a lofty goal like that seem achievable.’ While this could take a few years to achieve, let’s hope they do so sooner, rather than later.

 

Posted in 3D Printing Applications

 

 

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