Preterm labor is suspected to be triggered by inflammation caused by the fetus being sick. Researchers have proven this hypothesis by studying assumptions about the relationship between a mother and the fetus's health.
Dr. Ramkumar Menon and his team tested bioengineered exosomes as a delivery system for anti-inflammatory medicine directly to the fetus.
"Exosomes are natural nanoparticles or vesicles in our bodies, and we have trillions of them circulating through us at all times. By packaging the medicine inside a bioengineered exosome and injecting it into the mother intravenously, the exosomes travel through the blood system, cross the placental barrier and arrive in the fetus, where they deliver the medicine," explains Dr. Menon.
Several steps were taken before testing the drug delivery in mice. Fetal cells (immune cells in particular) can cause inflammation, the leading cause of preterm labor. The first step was to prove that these cells migrate the mother's uterine tissues.
Female mice were mated with male mice, who had been genetically engineered with a red fluorescent dye called tdtomato, to prove these cells' migration. The dye turns the male cells red, so after mating, cells in the developing fetus also turn red and can be easily tracked as they migrate through the mother. Dr. Sheller-Miller, first author, developed this model.
The next step involved using the mouse model to understand if bioengineered exosomes could deliver a special anti-inflammatory medicine, an NF-kB inhibitor, called super repressor (SR) IkB from the mother's bloodstream to the fetus. Results proved that the exosomes effectively delivered medicine to the fetus, slowing fetal immune cells' migration and delaying preterm labor.
Findings also showed that - a) to sustain the effects/delays in labor, repeated dosing was required. b) Prolonging gestation improved pup viability. c) Mouse models provide valuable information for understanding human mechanisms. d) Future studies and human clinical trials are needed to confirm results.
Dr. Menon says "Preterm birth rates have not reduced in the past few decades, and this technology (the bioengineered exosomes) could lead the way to other treatments for the delivery of drugs to treat the underlying cause of inflammation in a fetus." This technology can also be used to package other drugs in exosomes to treat other adverse pregnancy complications.