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January 28, 2021 /--- In a new study, researchers from the University of Texas Medical Branch in the United States may have paved the way for a new drug delivery system that allows doctors to treat "fetuses as patients", reducing the risk of premature birth and presecured birth.
study was published in the Journal of Science Advances on January 22, 2021 under the title "Exosomal delivery of NF-B inhibitor delays LPS-induced preterm birth and modulates femmune profile in cell cell models".
fetal macrophages are found in maternal tissue, pictured is Science Advances, 2021, doi:10.1126/sciadv.abd3865.
has long been suspected that premature birth is caused by inflammation caused by sick fetuses.
the new study, the researchers supported this hypothesis by studying several important assumptions about the healthy relationship between the mother and the unborn baby.
According to Dr. Ramkumar Menon, author of the paper and a professor in the Department of Obstetrics, Gynecology and Cell Biology at the University of Texas Medical Branch, his team worked with ILIAS Biologics, a South Korean biotech company, to test their bioengineered exosomes as a delivery system that delivers anti-inflammatory drugs directly to the fetus.
Menon explains, "Exosomes are natural nanoparticles or vesicles in our bodies, and we have trillions of exosomes circulating at any time.
by packaging the drug in a bioengineered exoded body and injecting it intravenously into the mother, the exosome passes through the blood system, through the placental barrier, into the fetus, where the drug is released.
" in laboratory tests on mice, there were several steps before testing the delivery of the drug.
First, Menon says, it's important to confirm that fetal cells, especially immune cells, actually migrate to her uterine tissue through the mother's body, which can lead to inflammation, which is the main cause of premature birth.
to confirm fetal cell migration to the mother, female mice mated with male mice, where male mice were genetically modified to express a red fluorescent dye called tdtomato.
this dye turns male cells red, so once mated, the cells of the developing fetus also turn red, so fetal cells can be easily traced as they migrate through the mother.
model was developed by Dr. Samantha Sheller-Miller, a postdoctoral researcher at Menon Labs and the first author of the paper.
model, they determined the process by which fetal immune cells reached maternal tissue, which was also a turning point in the study.
Once there was evidence of fetal cell migration, the researchers then used the mouse model to determine whether bioengineered exosomes could deliver a special anti-inflammatory drug---NF-kB inhibitor, SR I-B alpha--- from the mother's blood to the fetus.
bioengineered exosome was built using an innovative method developed by ILIAS Biologics called EXPLOR (Exosomes engineering for Protein Loading via Optically Reversible protein to protein interaction).
this study demonstrates that this bioengineered exogenation is effective in delivering drugs to fetuses, slowing the migration of fetal immune cells and delaying premature birth.
In addition, the study found that continuous effects/delayed childbirth required repeated dosing, that prolonged pregnancy increased survival rates in young mice, that mouse models provided valuable information to help understand mechanisms that are often observed in humans, and that further research, including human clinical trials, was needed in the future to confirm laboratory results in this study.
Menon said, "The rate of preterm birth has not decreased over the past few decades, and this technology (bioengineered exosomes) can lead to other treatments to deliver drugs to stop fetal inflammation."
" technology can also be used to package other drugs in the exosome to treat other adverse pregnancy complications.
results of this study are the second proof of concept, showing that ILIAS Biologics' bioengineered exosomes have significant anti-inflammatory effects.
April 2020, researchers at the Korea Institute of Advanced Science and Technology and ILIAS Biologics published a paper in the Journal of Science Advances entitled "Exosome-based delivery of super-repressor I-B-alsals sepsis-associated organial and mortality", showing that this bioengineered exosome has significant efficacy in sepsis mouse models.
(Bioon.com) Reference: 1. Samantha Sheller-Miller et al. Exosomal delivery of NF-κB inhibitor delays LPS-induced preterm birth and modulates fetal immune cell profile in mouse models. Science Advances, 2021, doi:10.1126/sciadv.abd3865.2.Hojun Choi et al. Exosome-based delivery of super-repressor IκBα relieves sepsis-associated organ damage and mortality. Science Advances, 2020, doi:10.1126/sciadv.aaz6980.3.Study proves potential for reducing pre-term birth by treating fetus as patient