In 2015, early in her pregnancy, Nicole Hashemi sought to understand the safe levels of caffeine consumption. Advised to limit her intake to reduce risks like miscarriage, Hashemi, an associate professor of mechanical engineering at Iowa State University, sought a more quantifiable measure. This quest led her to develop a simplified model of the placenta using microfluidic technology, aiming to demonstrate how substances move through and affect this vital organ.
Hashemi is among a group of researchers in the U.S. and abroad working on placenta-on-a-chip models. These models, as they become more refined, could revolutionize pregnancy studies by determining how drugs and toxins impact fetal development. “It’s going to be a game-changer for pregnancy studies,” said Ahizechukwu Eke, an associate professor of medicine at Johns Hopkins.
The placenta is crucial for fetal development, acting as a barrier against infections, delivering nutrients, and removing waste. However, studying the placenta in vivo is nearly impossible due to ethical and practical constraints. Pregnant women are often excluded from clinical trials to avoid fetal risks and potential legal issues for drug companies, leading to reliance on less reliable data from pregnancy registries, retrospective cohort studies, animal testing, and pharmacokinetic studies.
In 2022, Hashemi and her team received a three-year, $350,000 grant from the National Science Foundation to advance their placenta-on-a-chip model. This model uses microfluidic technology to replicate the placenta’s environment. The chip is a small, transparent silicone block with etched channels through which fluids flow, mimicking blood flow. One channel represents maternal blood flow, and the other represents fetal blood flow, with each lined with cells found in the placenta.
The initial success of Hashemi’s model in quantifying caffeine transport across the placental barrier demonstrates its potential. The model can also simulate higher blood pressure conditions, mimicking mechanical stressors like preeclampsia. In a 2021 study, Hashemi’s team used the chip to study the effects of naltrexone, a drug used to treat opioid addiction but not recommended during pregnancy. The study found that naltrexone caused the placental barrier to disintegrate, validating current medical recommendations against its use during pregnancy.
The technology, while promising, remains experimental. More data is needed before it can be approved by the FDA and used by pharmaceutical companies. “We can predict fairly accurately how nutrients actually get across the placental barrier,” said Dan Huh, a bioengineering professor at the University of Pennsylvania. Researchers hope that in the future, placenta-on-a-chip models can be used to study the effects of unknown drugs and environmental toxins.
The field of organ-on-a-chip technology has expanded since Huh and the Wyss Institute developed the lung-on-a-chip about 15 years ago. Researchers like Hashemi and Huh are now working to create more complex systems that replicate the human body’s environment more accurately. Despite the challenges, this technology holds great promise for improving drug safety and efficacy in pregnancy, ultimately benefiting patient care.
