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The 28-day menstrual cycle has been replicated in the lab for the first time, with the aid of “organ-on-a-chip” technology. Northwestern Medicine has developed a miniature female reproductive tract that fits in the palm of your hand and could eventually change the future of treatment for conditions such as endometriosis, cancer and infertility.
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The team, from Northwestern University, found that human reproductive tract tissues can be successfully cultured together with other tissues for a full month. They even released hormones, as in a natural cycle.
Teresa Woodruff, director of the Women’s Health Research Institute at Northwestern University, and colleagues generated a 'microfluidic' platform that can sustain five tissues together for a longer period of time than has been previously achieved. In the device, named EVATAR, fluid can flow over the tissues as they are tested at varying pressures, mimicking the natural dynamics that occur in vitro.
The EVATAR resembles a small cube and contains 3D models of ovaries, fallopian tubes, the uterus, cervix, vagina and liver. Each part of the system has a specially formulated fluid pumping through it, which performs the function of blood.
Woodruff and her colleagues were able to combine a mouse ovary with a human fallopian tube, endometrium (the membrane that lines the uterus), cervix and liver tissue. These reproductive tract tissues and peripheral organs integrated on the EVATAR to function in a 28-day cycle. Peaks of oestrogen and the suppression of progesterone were observed at different times in the cycle, as in a natural one.
"Ovaries don’t come out of young women so this [isn't] an option," Woodruff told WIRED. "That said, oestrogen and progesterone are identical small chemical molecules in humans and mice. So the effects of these hormones on the downstream tissue should mimic [that of a] human."
Microfluidics is still an emerging field in medicine. Allowing for research into microelectronics and molecular biology, the microfluidic system is capable of manipulating small amounts of fluids through channels with dimensions of tens to hundreds of micrometres. It has enabled the creation of synthetic systems that can mimic their counterparts in the human body.
However, developments in microfluidics have in some instances been hindered by the 'universal media problem' - the issue of creating a singular component to link each aspect of the system in a natural dynamic.
The team at Northwestern resolved this challenge by creating a variation of human blood - a universal medium that links all of the organs in the human body. Tissues in the system were then able to communicate through this medium.
The EVATAR offers unprecedented opportunities in the fields of personalised medicine, particularly those that can address the gender gap in pharmaceutical testing. Due to differences in the sexes in terms of organs and hormones, drugs can have drastically different effects in women compared to those found in men. It was only in 1993 that the FDA allowed women of child-bearing age in Phase 1 and Phase 2 drug trials. The ultimate goal of the EVATAR is to address this need by using stem cells of an individual patient to create a personalised model of their reproductive system, on which further medical treatments can be tested in depth.
Woodruff told WIRED that the EVATAR could form a platform for much-needed drug discoveries.
"We don’t have any way to model the intact female reproductive system," she explains, "so this will allow folks to study drugs in the context of the changing patterns of hormones. For example, new contraceptives, drugs that treat ovarian, endometrial or cervical cancer or fibroids and endometriosis. These are all future opportunities as the system is further developed."
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Growing human tissue in a lab is a process that often begins with individual cells, separated from other cellular mechanisms that are important for natural biological function. They are maintained on flat plastic, missing the chemical interaction, specific architecture and blood flow found in natural tissue. As a result, research using them cannot lead to the same outcomes as in the human body.
Personalised medicine is a vital way of testing how an individual reacts to certain drugs. Instead of a guessing game, or an endless list of possible side-effects on the back of medicine labels, microfluidic 3D systems could offer invaluable insight into the true effects of drugs within the human body. The EVATAR allows for organ–organ integration of hormonal signals in a manner that phenocopies the human menstrual cycle and pregnancy.
"Eventually we hope the ovarian cycle can be integrated with other tissues like heart and liver. This will allow drug discovery and testing on those tissues, but now in the presence of the changing hormones that are a part of normal cycles," Woodruff told WIRED.
The EVATAR project is part of a larger National Institutes of Health effort to create 'a body on a chip' in the US. The 'Tissue Chip' project aims to develop a comprehensive drug screening programme in conjunction with National Centre for Advancing Translational Sciences (NCATS). Organs such as the brain, heart and lungs could soon be replicated and tested upon using these microfluidic systems.
“If I had your stem cells and created a heart, liver, lung and an ovary, I could test ten different drugs at ten different doses on you and say, ‘Here’s the drug that will help your Alzheimer’s or Parkinson’s or diabetes,’” Woodruff says. “It’s the ultimate personalised medicine, a model of your body for testing drugs.”
The research is published in Nature Communications.
This article was originally published by WIRED UK
