Exosomes are nanoscale biological capsules that cells produce to protect and transport delicate molecules throughout the body.
The capsules are robust enough to resist enzymatic degradation, as well as acid and temperature fluctuations in the gut and bloodstream, making them a promising candidate for drug delivery.
However, harvesting them to achieve clinical grade levels of purity is a complex process.
“Exosomes are abundant in cow’s milk, but they are difficult to isolate from other proteins and lipids in milk,” said Rob Gourdie, professor and director of the Vascular and Cardiac Research Center to Fralin Biomedical Research Institute at VTC.
Gourdie’s lab has developed an evolutionary method to harvest exosomes from unpasteurized cow’s milk. Using this purification method, which was published this month in Nanotheranostics, the research team can extract about a cup of purified exosomes for every gallon of unpasteurized milk.
“For the first time, we have paved the way for the industrial scalability of exosome purification for oral drug delivery,” said Gourdie, who is also the Commonwealth Research Commercialization Fund Eminent Scholar in Heart Reparative Medicine Research and Professor of biomedical and mechanical engineering in Virginia Tech College of Engineering.
The research team has developed its cost-effective, multi-step purification process, which optimizes filtration methods and the timing of heat and chemical treatments affecting calcium levels, during the COVID-19 pandemic. Spencer Marsh and Kevin Pridham, both postdoctoral fellows in Gourdie’s lab at the Fralin Biomedical Research Institute, and Jane Jourdan, head of Gourdie’s lab, did the hands-on work to develop the proprietary procedure.
“Our team worked together safely and efficiently on this project throughout the pandemic,” Gourdie said. “It was a sight to see – their selfless teamwork, enthusiasm and dedication to overcoming challenges is something that doesn’t happen as often as you might think in science. There were many failures, but eventually we found some staged processes that worked. “
Joy Wolfram, an assistant professor of medicine at the Mayo Clinic, who was not involved in the study, says the new protocol advances the pharmaceutical potential of exosomes.
“What is remarkable is the amount of extracellular vesicles they are able to produce. Isolating and fabricating extracellular vesicles in an evolutionary manner has always prevented their translation in the clinic, but this article shows a way to overcome these obstacles, ”said Wolfram. Wolfram previously published a protocol for using tangential flow filtration technology that Gourdie’s team adapted to isolate exosomes from milk.
Exosomes are naturally secreted by almost all types of cells in humans and other mammals, and can be found in abundance in blood, lymph, urine, and milk. Lined with protective membranes, exosomes carry biomolecules, fragments of genetic material and chemical signals between cells over long distances.
Over the past decade, research into their pharmaceutical applications – especially for delivering fragile drugs, such as peptides and microRNAs – has exploded.
“Imagine that instead of getting the vaccine, your nurse hands you a milkshake instead. Another milkshake may contain exosomes loaded with a therapeutic peptide designed to protect internal organs such as the heart against myocardial infarction, ”Gourdie said.
Exosomes can also enter the blood-brain barrier, a set of coupled cellular processes that protect the brain from pathogens and unwanted chemicals, ushering in a new way of delivering treatments to treat neurological diseases and brain cancer.
“Improving the viability of using exosomes opens up a wide range of drug delivery methods with limitless clinical applications,” said Gourdie.
Gourdie partnered with Homestead Creamery, a local dairy processing plant, to obtain unpasteurized milk samples for the study.
“We’ve always built our business on relationships, and it’s an exciting collaboration for us,” said Donnie Montgomery, Co-Founder and Co-Owner of Homestead Creamery.
Last year, Gourdie granted the intellectual property to administering medication to the heart using exosomes via Virginia Tech LICENSE: Technology Commercialization Center and formed The Tiny Cargo Co.