Scientific Advancements

If Wiwatpanit's team is able to successfully combine organoids into systems, future biomedical researchers would have broadened experimental capabilities for any variety of research topics.

Fighting the Zika Virus

In February 2016, the World Health Organization declared the Zika virus a Public Health Emergency
of International Concern. The Zika virus, which saw local transmission in the United States in 2016 and 2017, is transmitted primarily through mosquitoes. While those infected with the Zika virus are generally asymptomatic or show only mild symptoms, a pregnant adult can transmit the virus to the growing fetus. This transmission can cause infants to be born with microcephaly and other congenital malformations and neurological complications, and is also associated with pregnancy complications including preterm birth and miscarriage.

The Zika virus has been recorded in 87 countries and territories across the world, and outbreaks have become more frequent over the last two decades. In Thailand, cases of Zika virus have been reported for the past 16 years in low numbers. Wiwatpanit points, though, to the ripe conditions in Thailand for a full-blown Zika epidemic. "We have all the factors here in Thailand," he says, "and it's better to be prepared."

Wiwatpanit's team uses samples of cells from a uterus to create what he calls a "mini organ" in a dish. This organoid mimics the layers of cells in the uterus. The team is also able to cause the organoids to mimic different stages of the menstrual cycle and pregnancy. Then, the team infects the organoids with the Zika virus at various stages of the menstrual cycle and pregnancy to study at which point the uterus is most likely to become infected. Wiwatpanit's team, he says, is also attempting to engineer a system that mimics the placenta, so that it can study the transmission of the Zika virus across the placenta from mother to fetus.

The team's work also looks at a specific class of antibodies that have been shown to neutralize the Zika virus in other systems, like kidney cells. "Those systems are not directly relevant to moth- er-child transmission," Wiwatpanit explains, "so this would be the

first time that we look into how to use this antibody to neutralize the process of mother-to-child transmission."

"We're hoping that we can use this knowledge to develop future treatment for the Zika virus," Wiwatpanit says. "Can we apply this antibody to the mother to prevent transmission? Can we even develop vaccines? Can we treat the mother to protect the fetus? This research will be the base for the development of a bunch of therapeutics for the Zika virus."

System of Organoids

Another exciting aspect of Wiwatpanit's research is the potential to combine an organoid mimicking the uterus and an organoid mimicking the placenta into a combined system. Wiwatpanit notes that most diseases affect multiple systems in the body. "We [the bioengineering research field] have mini brains now," he says. "We have intestines, we have the uterus. I think the field is moving in the direction of putting different types of organoids together to see how they interact with each other."

If Wiwatpanit is able to culture cells from a placenta and create a two-organoid system, his team will be able to study both the maternal compartment and the fetal compartment moving forward. This, he says, will enable disease modeling or drug testing.

"If we can engineer a system that mimics the placenta with the maternal and fetal compartments all together, this can be used to research more than just the Zika virus," Wiwatpanit explains. "We can also use this system to study other diseases that are capable of being transmitted from mother to child, like HIV. We can also use this system as a platform for drug testing, or to develop therapeutics intended for use during pregnancy. We can do toxicology studies to see if substances, or drugs, or even nutrients or supplements can be transmitted through the placenta from mother to child."