EVATAR is a female reproductive system that fits in the palm of the hand.
(Courtesy of Northwestern Medicine)
The so-called “organs on a chip” — small clumps of tissue growing in lab dishes that mimic the function of their human counterparts — a promise for basic science and the development of medicines. And these efforts are scaling up. On Tuesday, scientists unveiled a five-organ of the female reproductive system on a chip small enough to fit in your hand, and showed that it could simulate a 28-day menstrual cycle.
The chip is part of an effort funded by the National Institutes of Health to build a fully human body-on-a-chip — a creation that would involve all the organ systems and the investigators to perform unprecedented accurate experiments on the human tissue. Other research groups are also working on the chips that mimic multiple organs, e.g. the liver, the heart and the blood vessels.
In this case, the “chip” is about the size of a hardcover book, and littered with Lego-like blocks, each of which is hollowed out and keeps pieces of tissue grows on plastic scaffolding: ovary, fallopian tube, uterus, cervix, liver. (The ovary samples come from mice ovaries are rarely removed from healthy women, while the tissue for the fallopian tubes, the uterus and cervix comes from women who hysterectomy.) The blocks are connected by tiny tubes to simulate how the real bodies communicate with each other in the human body.
Those tubes allow the hormones to flow between the miniature organs. By feeding the correct cocktail of hormones in the ovaries and block, the researchers were able to coax and the small organ to release of an egg, and to produce hormones that flowed in each organ downstream, causing them to behave similarly to how they do in the human body.
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This is the first menstrual cycle “on-a-chip,” said Teresa Woodruff, the study of the primary researcher and professor of obstetrics and gynecology, Northwestern University Feinberg School of Medicine.
The results were published on Tuesday in Nature Communications.
Everything about EVATAR
The chip called “EVATAR,” a portmanteau of the biblical “Eve” and a representative of ‘avatar’ could ever be used for testing the effects of drugs on human tissues before you put them in the human body. Now, animals, play that role — but scientists wonder whether the animals have different physiology would be a reason why so many drugs never make it in the clinic.
The build of the EVATAR was a team effort, with multiple groups working on the construction of the organ systems, and a crack team of biomedical engineers in Cambridge, Mass., the handling of the design of the chip itself.
Jonathan Coppeta, a biomedical engineer at the Charles Stark Draper Laboratory, was part of that team, which built pipes to move fluid between the organ blocks. It is governed by a 62-pumps which can be switched on or off. Each of these pumps used a pinky-sized electromagnet to move about a millionth of a liter of fluid per time.
Such a precisely adjustable system allows scientists to do things that wouldn’t be possible to do in a real person, such as the change of the speed at which the hormones flow from one organ to the other, to study the effect of this hormone on the organs.
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But because it was still early in the organ-on-a-chip development, there are plenty of unknowns. The researchers will inevitably be confronted with the question: If it doesn’t kill the chip, it means that the safe is in a person?
“Would it be possible to be better than an animal model,” said Jeffrey Borenstein, a biomedical engineer at Draper. “Yes, because you are using human stem cells. Is it perfect? No, because there are always restrictions.”
Reproductive biology researchers affiliated with the project noticed a certain constraint in the team model of a uterus. The lining of a human uterus mainly consists of two types of cells — but on the chip it is especially a type of cell, former Warren Nothnick, vice-chairman of the department of molecular and integrative physiology at the University of Kansas Medical Center. Nothnick said that may form a barrier for the system is the human truth, because the under-represented cell type gives rise to colon cancer. But on the whole, he said, the paper is “truly groundbreaking.”
Dr. Julie Kim, a Northwestern professor who led the team to the uterus block, said that the promotion of this special type of cells known as the endometrial cells grow well in the lab-built organs is a challenge. She hopes to build more life-like os in the future: “My dream is to be a menstruating uterus in a court.”
Pharma showing interest
One of Woodruff ‘ s next steps is the building of personal EVATARs, of which the miniature organs are grown from the stem cells of individual people. That researchers could test how a drug would have an impact on a certain person, based on their biology.
Men have to wait, but maybe not for long, within a year, Woodruff hopes to have more results to share about the male version of the project, nicknamed ADATAR.
All pharmaceutical companies are starting to show interest — Woodruff said that they already tested some of AstraZeneca candidate to measure their influence on the female reproductive system.
Draper, the chip offers support for a maximum of 12 bodies, so that the researchers can make use of this chip to simulate different organ systems. The lab is also using similar technology to build custom chips for pharmaceutical companies such as Pfizer.
Meanwhile, Woodruff is looking for participants to stem cells, which can be used to create custom organ systems, which she said should happen in the coming year.