Israel, US researchers create 'mini Human-on-a-Chip' to speed up drug t... https://www.timesofisrael.com/israel-us-researchers-create-mini-human...

Israel, US researchers create ‘mini Human-on-

a-Chip’ to speed up drug testing
Tel Aviv and Harvard University scientists have created and linked up nine Organs-on-a-chip, including brain,
heart and liver, paving way for personalized drug development

By SHOSHANNA SOLOMON 
27 January 2020, 6:02 pm

Researchers at Harvard University and Tel Aviv University develop mini human organs on a chip to help with drug development. Nine organs were constructed as 'Organs-on-
a-Chip.' (Wyss Institute at Harvard University)

In what sounds like something straight out of science �ction, Israeli and US researchers say they have created nine
different mini human Organs-on-a-Chip that will pave the way for researchers to test out drugs as if on humans. Not
only that: the researchers also managed to connect the nine Organs-on-a-Chip they have developed — including a
Brain-on-a-Chip, a Heart-on-a-Chip and a Liver-on-a-Chip — creating what they call a “mini Human-on-a-Chip.”

Two new studies by researchers in Tel Aviv University and Harvard University on the subject were published in the
journal Nature Biomedical Engineering on Monday.

Organs-on-a-chip were �rst developed in 2010 at Harvard University. Then, scientists took cells from a speci�c
human organ — heart, brain, kidney and lung — and used tissue engineering techniques to put them in a plastic
cartridge, or the so called chip. Despite the use of the term chip, which often refers to microchips, no computer parts
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What is new in the two studies published on Monday is the fact that the researchers have now managed to link-up the
various organs, and have proven that these can react to drugs in the same way as human organs would in a clinical
trial, said Dr. Ben Maoz of Tel Aviv University’s Department of Biomedical Engineering and Sagol School of
Neuroscience in an interview with The Times of Israel.

Dr. Ben Maoz of Tel Aviv University’s Department of Biomedical Engineering and Sagol School of Neuroscience; 4 April 2019 (Yonatan Zur)

When developing drugs, researchers try them out �rst on rodents and only then, if successful, on humans. But some
60%-90% of the drugs that are successful in rodents fail in humans, explained Maoz, a co-author of the studies.

This makes the process of drug development very long and expensive, he said. Ideally one would want to cut out the
rodent stage and get to human testing directly, for quicker results. That of course is impossible. Until the two new
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studies.

Indeed, a team of 57 scientists at Tel Aviv University and Harvard and other research entities and drug developers,
worked for seven years on a project to develop what they call “a functioning comprehensive multi Organ-on-a-Chip
(Organ Chip) platform” that reacts to drugs just as real humans would react to them in a clinical setting.

“We created a human model that is not a human being,” said Maoz, who co-authored the studies on the subject with
Prof. Donald Ingber, the founding director of Harvard University’s Wyss Institute for Biologically Inspired
Engineering, and with the Wyss Institute’s Prof. Kevin Kit Parker.

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The scientists did this by taking human cells and through tissue engineering managed to mimic the functionality of
the organ from which the cells were taken — like the liver or the heart — within a plastic cartridge the size of a USB
�ash drive.

The kidney acts as a �lter, and the heart acts as a pump in the body, Maoz explained. So the researchers managed to
tissue engineer the human kidney cells to work as a �lter within the plastic cartridge, creating a “Kidney-on-a-Chip,”
he explained. Likewise, for the heart. The scientists managed to make the human heart cells contract within the
cartridge, creating a Heart-on-a-Chip. And the same procedure was performed on other organs and parts: the liver,
the brain, the blood brain barrier, the lung and bone marrow, skin, and the intestine.

Not only that. The scientists created a so-called Interrogator, a robotic liquid transfer device to link individual “Organ
Chips” with each other, in a way that mimics the �ow of blood between organs in the human body.

“We created a unique machine that connects between the nine organs, the brain, the lung, the bone marrow, and
others, like a ‘lego,’ to create a mini ‘Human-on-a Chip’,” Maoz said. The linking system they created was tested
successfully for at least three weeks, the Tel Aviv University said in a statement.

The researchers then tested their Organs-on-a-Chip with two drugs: a drug to combat intestine in�ammation and a
cancer drug. Their study showed that when the drugs were injected into the new system, the Organs-on-a-Chip
reacted and responded to the medications just as real human organs did in clinical trials with the drugs.

“We were able to create nine unique human organs [on a chip] and connect between them and show that what you
put in the system is comparable to human clinical data,” he said.

To get to this point was not easy and there were “many challenges on the way” that had to be overcome, Maoz
explained. For example, real human organs live off oxygen supplied to them by human blood. So the researchers had
to develop a way to feed their cells in a chip and devised an arti�cial blood — made-up of different chemicals,
minerals, vitamins and hormones and other components, that fed the cells in the chip.

Also, whereas in a human organ there are billions of cells, the Organ-on-a-Chip just has thousands of cells — so the
researchers had to develop computational models to overcome the size problem and ensure that the cells function
like those in a real organ, even while on the chip.

So, what now? “There are millions of directions we can take this,” Maoz said by phone. “Hopefully one day people
will be able to use this to test drugs instead of animal models,” he said, serving as an alternative to animal
experiments and cutting back on their suffering. Another application could be to use the system to create
personalized mini Organs-on-a-Chip — each person with their own cells and organs, to test how they would react to a
particular drug.

“We could create a ‘mini me-on-a-chip’,” he said. This would help save time and pain of experiments. “The dream is
to expedite and personalize drug development.”

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