In Dr. Quinton Smith’s lab at the University of California, Irvine, miniature models of human placentas could hold the key to understanding and treating preeclampsia, a common but potentially life-threatening condition that can occur during pregnancy.
Preeclampsia occurs when the placenta—the organ grown in the uterus that delivers oxygen and nutrients to developing fetuses via the umbilical cord—can’t function properly. The condition affects about 5% to 8% of pregnancies. And, according to the Preeclampsia Foundation, the rates among Black women are 60% higher than those among White women.
Still, despite the disorder’s prevalence, its origins have eluded scientists for decades. Few successful methods for detecting and treating preeclampsia—characterized by high blood pressure, protein in urine, and, in more extreme cases, organ damage—exist today.
Recognizing a need for a new way to study this condition, Smith, a 2023 Pew biomedical scholar, combined his extensive background in biomedical engineering with basic science research to pioneer a method for constructing what he refers to as “self-assembled miniature placentas” in the lab.
“What if we can actually create placenta cells in a dish, look at their interactions with blood vessels, and maybe discover new biomarkers that are secreted by the placenta that might be an earlier indication of the disease?” said Smith, who is an assistant professor of chemical and biomolecular engineering at Irvine.
Biomarkers are molecules, often measurable through simple lab tests, that help scientists detect disease. Preeclampsia usually goes undiagnosed until 20 weeks into pregnancy and the only cure is delivery, so finding a biomarker could help identify the disease earlier and potentially inform new ways to treat it.
The emergence of new scientific tools over the past decade helped make these miniature placenta models possible.
“We now have technology where we can take a skin cell, for example, and we can reprogram it all the way to an embryonic state,” Smith said. “And we can turn those cells into placental cells.”
To create the models, the lab cultures stem cells in a three-dimensional environment and uses a “chemical cocktail of factors” to encourage conditions that replicate the cellular structure and function of a human placenta. The organoids even secrete human chorionic gonadotropin or hCG—the chemical that triggers a positive pregnancy test.
Once the organoids are constructed, the team creates what are known as “organs on a chip” to control interactions between cells. This innovative platform scales down traditional lab approaches using petri dishes and manual labor so scientists can mimic biological environments remotely using a computerized chip. With this technology, Smith and his team can fabricate architectures at resolutions smaller than the size of a human hair to precisely create cellular arenas to study organoid behavior in controlled microenvironments.
“So we take our placental organoids, and then we grow human blood vessels in these little chips and look at how the placenta impacts how those vessels function,” Smith explained.
Understanding how placental cells interact with blood vessels is key to getting to the root cause of preeclampsia. Many scientists theorize preeclampsia starts with improper placenta formation and is closely linked to the dysregulation of a process called spiral arterial remodeling. This crucial step in placenta development happens during implantation, when specialized cells lining the edge of the embryo—called trophoblasts—invade small arteries in the uterus.
These trophoblasts connect the placenta to the mother’s own vascular system, creating a temporary “plug” that redirects some of the mother’s blood flow into the placenta itself. But when this process is compromised, the placenta doesn’t get the nutrients it needs and secretes factors in the uterus that eventually trigger preeclampsia.
Until recently, there wasn’t a way for scientists to easily examine this process. Most biomedical breakthroughs start with animal models. Researchers often design studies using model organisms such as mice or fish because their genetic similarity to humans allows for easy and safe experimentation. Spiral arterial remodeling, however, can’t be easily replicated in animals, so the Smith lab’s meticulously crafted organoids represent a first-of-its-kind opportunity to watch this process unfold in real time.
“As we’re growing these mini placentas, we can add stress hormones or microplastics. We can add all these little variables and test them. And maybe we can understand how these placental cells change and why they secrete all these different factors,” Smith said.
Although the lab hopes these models will help eventually uncover findings about how preeclampsia works at a cellular level, the mission extends beyond that.
“Maternal-fetal health is understudied compared to other diseases. And there’s a huge health disparity when it comes to different races,” Smith said, adding that the gaps are particularly stark when it comes to Black mothers.
“That’s what really motivates me, this love of how blood vessels function, but also this important idea of studying health disparities—studying things that might be understudied and applying my interest and tool set to this problem,” Smith said.
Smith also hopes this work can inspire more researchers to look to stem cells as a path to discovery.
“I’m really hopeful that this pushes the idea that we can actually use in vitro systems with human cells as a way to predict and model some of these diseases,” he explained. “Big picture, can we show that we can actually use human cells as a better model system?”
Donna Dang works on The Pew Charitable Trusts’ biomedical programs.
