Penn State scientists have developed an innovative bubble-based method for observing immune cell activity. Macrophages are tiny but essential cells in the immune system that hold promise for cell therapy for a variety of health conditions. Realizing the full potential of macrophage therapy depends on our ability to observe their activity in the body. Now, it's possible for Penn State researchers to develop a way to monitor the activity of these cells.
Research details and the importance of macrophages
In a study published in the journal Small, Penn State researchers report a novel ultrasound imaging technique that can continuously observe macrophages in mammalian tissues, with potential future applications in humans.
"Macrophages are immune cells that are important in nearly every function of the immune system, from detecting and clearing pathogens to wound healing," said corresponding author Scott Medina, William and Wendy Cobb Early Career Associate Professor in the Department of Biomedical Engineering. "It's a component of the immune system and is a real bridge between two types of immunity: innate immunity, which responds to things very quickly but not very precisely, and adaptive immunity, which is much slower to kick in but responds much more precisely."
Macrophages can regulate these two branches of the body's immune response and help the body achieve functions such as anti-infection and tissue regeneration. On the other hand, they also help mediate inflammation associated with injury and conditions such as diabetes and rheumatoid arthritis. Medina believes these cells could be harnessed and applied to treat diseases such as cancer, autoimmune diseases, infections and damaged tissue. This therapy would involve isolating, modifying, and/or engineering macrophages to enhance their properties in fighting disease, controlling immune responses, and promoting tissue repair.
"If we can visualize the activity of these cells in the body in real time, then we can learn a lot about how disease develops and how healing occurs," Medina said. "This will allow us to see the activity of cells in the body, because right now, we can only take cells out of the body and see their activity in a dish, and that is not the same behavior as what we see in the body."
Ultrasound imaging technology
The researchers turned to ultrasound imaging, a common technique for looking at tissues inside the human body. However, using ultrasound alone, macrophages mingled with their fellow cells.
As many home cooks know, emulsions are a mixture of oil droplets suspended in a liquid like vinegar or water, used to make salad dressings; nanoemulsions mean those oil droplets are so tiny, only nanometers in diameter. "In ultrasound imaging, macrophages are essentially invisible because you can't tell where these cells are relative to all the other cells in our tissue. They all behave the same, so you can't really see specific cells. We have to create what's called a contrast agent, something that can label the cells we're interested in and then provide some contrast in the image that's different from the background. That's where these nanoemulsions come in," Medina said.
Researchers used nanoemulsions to create more elastic bubbles. Bubbles reflect ultrasound sound waves very effectively; however, if someone injects the bubbles into a patient, the effect is not as good because the bubbles burst quickly.
"We needed a way to allow bubbles to form while imaging, rather than before, while also allowing these bubbles to persist as long as possible," said Inhye Kim, a postdoctoral fellow in biomedical engineering and first author of the study.
The researchers introduced nanoemulsion droplets into cells, which internalized them. Under the action of ultrasonic waves, the liquid droplets undergo a phase change and become gas, thus creating bubbles. This change is facilitated by the pressure generated by ultrasonic waves, which push and pull the droplets as they oscillate, using pressure to force the droplets to boil, causing them to vaporize and turn into bubbles.
"It's similar to how at higher altitudes like Colorado, water boils at a lower temperature because there's less pressure to stop it from boiling," Medina said. "We put pressure on the droplet through ultrasound, effectively making it boil when we want it to, so that it vaporizes and forms bubbles."
Research results and future applications
They tested the new technique on tissue samples from pigs and found that imaging macrophages was effective. Medina said that this method allows researchers to continuously observe the activity of immune cells in the body, leading to a better understanding of how the immune system is regulated and its role in fighting disease. Among other things, this approach could help develop better immune cell therapies for patients in the future. For example, for cancer patients, this research could make macrophage therapy more effective with fewer, milder side effects.
Next steps in the research include exploring the possibility of using this technique to visualize other types of immune cells in the body, or to monitor plaque buildup in arteries. In addition, the researchers are seeking collaborators to advance the technology.
The researchers hope to collaborate with others in the field of immunology research who have special interests and may find this technology useful, and are open to further collaborations and applications.