The female menstrual cycle is a rite of passage into womanhood that for centuries has been shrouded in mystery and taboo. Pliny The Elder, for one, believed that menstrual blood could turn crop fields barren. Just last century, one scientist floated a theory that menstrual blood contained a poison that caused women to turn wine into vinegar. Let’s not even start on the rumours that a burnt toad can ease a heavy flow.
Now, as though peeling away the mystique of womanhood once and for all, scientists at Northwestern University have used tissue cultures to create a miniature 3D model of the female reproductive tract: ovaries, fallopian tubes, and other reproductive organs, connected together to mimic the functions of a 28-day menstrual cycle. This particular rendering of female sexuality, described in a paper published Tuesday in Nature Communications, is encased in plastic and not much bigger than an iPhone Plus.
It is, in essence, a period in a petri dish. And scientists hope that it might unlock a more detailed understanding of the female reproduction system and the diseases that plague it, as well as eventually paving the way for personalised treatments designed to reflect a woman’s individual biology.
“This is very exciting,” said Christos Coutifaris, president-elect of the American Society of Reproductive Medicine, who was not associated with the research. “In the short term, it could allow us to understand a lot more about person-to-person variability in the body. In the long term, this is a step towards individualised medicine.”
The period-in-a-petri-dish is not the first attempt to model the organs of the human body in miniature form using cellular cultures. It was part of a larger effort spearheaded by the National Institutes of Health to recreate the entire human body on a “chip.”
For every secret that science has revealed about our biology, there are hundreds more unknowns. Testing drugs on animals or human cells in a petri dish can only tell us so much about how those drugs might actually perform in the human body, and real organs are far too valuable as transplants to be used in experiments. This is where so-called “organs-on-chips” come in. By replicating many of the functions of human organs in miniature, on microchips, scientists can, in theory, more accurately observe what happens to those organs when exposed to different drugs or environmental conditions.
A time lapse of the period-on-a-chip system in action. Image: Northwestern
Back in 2010, a scientist at Harvard’s Wyss Institute developed the first organ-on-a-chip, a lung. Since then, scientists have successfully made thumb drive-sized models of the lung, liver, kidney, heart, artery, bone marrow and cornea. In each case, tiny microfluidic tubes are lined with cells taken from the organ of interest and arranged within the chip to mimic some of the key functions of those organs. When nutrients, drugs, bacteria or other test materials are run through the tubes of the chip, scientists are able to closely observe how specific cellular processes respond. In 2015, for example, Michigan State University scientists used a chip to model how endocrine cells secrete hormones into the blood stream in order to test a diabetes drug.
Organs-on-chips have recently seen a major boom in interest. In 2014, the NIH doled out $17 million in grants for its Tissue Chip for Drug Screening program to 11 institutions, a second wave of grants after funding 19 other research organisations to do tissue chip research in 2012. DARPA has its own separate tissue chip program. Increasingly, drug companies are turning to tissue chips to test new drugs, too.
The problem with the organ-on-a-chip, though, is that it only allows researchers to observe one organ at a time, rather than an entire physiological system. The period-in-a-dish is the next step up. It allows researchers to observe how different stimuli impact not only the ovaries or the uterus, but the entire reproductive system at once.
“Our biggest challenge was in some ways just building the technology,” said Teresa Woodruff, the study’s lead investigator and director of the Women’s Health Research Institute at Northwestern. “You can’t model everything that happens in the reproductive system on a single chip. This is a new way of looking at cell function.”
The period-in-a-petri-dish, called Evatar, looks more like a set of sad Lego bricks than anything distinctly biological. Each “organ” occupies its own muddy brown cube, linked together by tubes that pump fluid between them. Cultured ovarian follicles produced the hormones in this synthesised system to regulate tissue function over a 28-day cycle, causing fluids to move through the organs. One of the biggest hurdles was designing a medium that could flow through all of the system’s components, acting as blood does in the body.
“Our body is composed of a lot of different cells and all those cells are in communication,” Woodruff told Gizmodo. “We’re basically modelling that. It’s not an exact organ, but it is a good organ mimic.”
The hope is that this work will allow researchers to do a whole lot more than simply test new drugs more efficiently, though that’s definitely an important part of the work. In the paper, researchers detail the creation of a model using mouse cell cultures, but in the not-too-distant future the same approach could be used to create models of various human reproductive diseases in order to better study them. It could also allow researchers to study the differences between individuals at a functional level, one day leading to personalised therapies.
“The importance of this is that not everybody is the same,” Coutifaris, of the ASRM, said. “We’re not an inbred strain of mice where every mouse reacts the same to a drug, or a hormone or whatever. The next step is to understand the differences from woman to woman [and] how they might respond to things like drugs.”
Why, for example, does one combination of drugs result in successful in-vitro fertilisation in one woman, but not another? Why are certain women more susceptible to ovarian cancer? Which birth control is right for you? Science doesn’t really offer much more than guesstimates to these questions. Organs-on-chips might at least be able to offer a little more data to base those decisions on. Using a woman’s stem cells, for example, a doctor might one day create a personalised model of her reproductive system, test a bunch of different fertility drugs on the model, and from those tests select the drug most likely to result in healthy eggs, hopefully saving her time, money, and the emotional stress of many rounds of IVF.
Woodruff said the next step is to enhance the model of the female reproductive system, and to design a male counterpart. Eventually, many of these chips might be used in tandem to understand how a drug, for example, can impact all the systems of a person’s body.
Coutifaris cautioned that for now, these advancements are most useful for research. Creating personalised drug treatments using custom-built miniature organs on a chip, he said, is a long way off.
“It’s important to be careful about expectations. There is still a lot of work to be done here,” he said. “But even though those things are far-fetched at present, we need dream.”