Organs-on-a-chip: revolutionizing medicine

The human body on a microchip may be the future of biomedicine. Scientists the world over have already begun to develop micro-scale models of organs such as the heart, lungs and liver. The aim is to replace testing on animals, and improve the accuracy of the models. One of the researchers is Maria Tenje, who has been admitted as a Wallenberg Academy Fellow, and is now busy developing a lifelike model of the blood-brain barrier.

Maria Tenje

Associate Professor of Engineering Physics

Wallenberg Academy Fellow 2016

Institution:
Uppsala University

Research field:
Microsystems technology

The marriage of microsystems technology with life sciences is described as a revolution in the field of biomedicine. It is a rapidly growing area, offering new tools and more accurate models as we try to understand the body’s various organs. Ultimately, it may lead to new and better therapies for a wide variety of diseases.

“The new testing systems also enable us to do fewer experiments on animals,” says Tenje, who is Associate Professor of Engineering Physics at Uppsala University.

“At present many new drugs are tested on animals, particularly mice, and large numbers of them are needed. We also know that animal models only tell us how drugs work on animals, which may not be the same thing as how they work on humans.”

Even now, efforts are under way at various institutions to develop models of human organs using microsystems technology. These models are known internationally as organs-on-a-chip. Tenje has chosen to specialize in a field where the technical challenges are particularly refined.

“We’re dealing with biological barriers, such as the skin, lungs and blood-brain barrier – those parts of the body that separate the inside from the outside. This is where I think our technical expertise will be able to make the biggest contribution.”

The project is focusing on developing an artificial model of the blood-brain barrier, which protects the brain from harmful substances in the blood. It consists of a large number of cells that combine to create semi-permeable walls in the brain’s network of capillaries. The barrier contains molecules that bind to the substance of various structures. They can be likened to guards whose task is to eject unwanted guests and throw them back out into the bloodstream. This sometimes include substances ingested in food or drink that must be prevented from entering the brain.

New potential for treating brain disease

The blood-brain barrier is essential, but its efficiency is also an obstacle when administering drugs to treat diseases such as Alzheimer’s and Parkinson’s. A more lifelike and accurate model of the blood-brain barrier would therefore be a new and better tool for trying out candidate drugs. A model of this kind might ultimately play a crucial role in the fight against neurodegenerative and mental diseases.

“We know this will be even more important to enable us to try out the next generation of major protein-based drugs requiring active cell transport.”

Thanks to her admission as a Wallenberg Academy Fellow, Tenje has been able to put together a research team comprising the necessary broad know-how and expertise. Her colleagues include an electrical engineer and specialists in microfluidics, biotechnology and biomedical technology. The team is also collaborating closely with researchers in the biological and medical fields.

“First and foremost, admission as a Wallenberg Academy Fellow has given me the opportunity to realize my visions. I have been able to recruit four researchers/doctoral students from different backgrounds and with different expertise. It is fantastic to be able to create a team capable of achieving success. Becoming a Fellow has also given my confidence a great boost.”

Like a sandwich cake

The experimental work is taking place in the laboratory clean room, where the researchers are using microtechnology and hydrogels (natural polymers) to build a three-dimensional scaffold integrated with microfluidic channels to provide the cells with nutrients. There are six to seven cell types in the blood-brain barrier; in the 3D model they can be grown layer on layer, moving with the same freedom as in a real brain. Tenje likens it to a cake:

“The unique feature is that we can build a laminated structure made up of the various cells regulating the barrier. Imagine a base of a layer of jelly consisting of endothelial cells. Then we add a layer of butter cream containing another cell type. The next layer contains the pericytes, and so on.”

The result is a highly lifelike model, in which even the thin, biological materials resemble those found in the brain. This is a substantial improvement on the cell culture plates currently used as model systems, which only allow study of two cell types at a time on hard membranes, which also have no contact with each other.

Modeling the entire body

The technology is still in its infancy. One long-term aim is to connect up miniature versions of the various organs to provide a systemic understanding of the body. The field is a growing one, and Tenje, together with fellow researchers in Germany and Austria, will be starting a series of European conferences, beginning in Stuttgart in 2018.

Tenje is surprised to find herself in her present position.

“Actually, my background is not an academic one, although I’ve always enjoyed solving problems. And whenever I’ve had normal jobs, I’ve been bored. That’s why I returned to the academic world as soon as I could. Now I’m driven by curiosity, but also by the desire to see my research make a difference to people – maybe not in five years, but sometime in the future. And technological breakthroughs sometimes happen more quickly than anyone expected.”

Text Nils Johan Tjärnlund
Translation Maxwell Arding
Photo Magnus Bergström