UC engineering researcher studying exosomes for potential nerve regeneration awarded $2M NIH grant

Leyla Esfandiari, an associate professor of biomedical engineering at the University of Cincinnati, has received $2 million from the National Institute of General Medical Sciences to fund her research on small extracellular vesicles called exosomes and the role they play in nerve regeneration as treatment for nerve injuries or other neurodegenerative diseases.

Esfandiari has been studying exosomes for several years. In 2018, her team developed a new lab-on-a-chip device that uses circulating exosomes for noninvasive point-of-care screening. The device extracts exosomes from biofluids in an expedited and cost-effective manner and it was granted a patent in January 2023. That project was partially funded by the National Science Foundation CAREER grant in 2021.

“Previously, we made the device that can help to purify exosomes from biofluids like blood or saliva. We can now extract and purify these vesicles that are secreted from any type of cells and further utilize them for either diagnostic or therapeutic applications,” Esfandiari said. “This NIH award is a great opportunity for us to start a new venture on investigating the role of exosomes as new therapeutics for nerve regeneration. We are combining the technologies that we developed in our lab to tackle a new problem in medicine, which is regeneration.”

The study of extracellular vesicles is a relatively new field as they were discovered only 40 years ago. At first, they were seen as the garbage bin of cells, simply cycling out the unwanted information. However, once scientists dug deeper into these small vesicles, they quickly realized their impact as carriers for circulating biomarkers.

It is now known that exosomes are important vesicles for cell-to-cell communication. They circulate in the body, and contain messages through micro-RNAs, proteins and lipids. When they are released by cells, they travel through biofluids or pass through tissue and can pass their contents into the recipient cell, therefore changing its genetic coding or function.

The team is researching whether these vesicles will have a different genetic coding once electric fields are applied to their parental cells, thus having the ability to pass the new coding on to its neighboring cells. More specifically, if the micro-RNAs are helping with the regeneration of neurons, they could potentially be used in treatment for nerve injury or neurodegenerative diseases.

The inspiration for this work came from Esfandiari’s existing knowledge about the field of exosomes and her interest in the bioelectric signaling in the body.

“We knew that endogenous electric field affected neurons and helped with neuroregeneration, and that was a nice starting point,” Esfandiari said. “We are putting together everything that we already know and have experience with, to find the answer to a new question.”

The grant is a Maximizing Investigators’ Research Award for Early-Stage Investigators. An “early stage” investigator is anyone within 10 years of earning their doctorate, making this a unique opportunity for many junior faculty.

“This grant gives you freedom to explore your research in new ways, and the opportunity of investigating new directions if you find interesting results which you didn’t expect, and that’s the beauty of science,” Esfandiari said.

Esfandiari believes that data can tell a story and encourages her students to investigate it with an open mind, curiosity and persistence. Her team consists of four doctoral students, one master’s student and one research associate. Each has different backgrounds, skillsets and interests, creating diversity within the group. For instance, the research associate on Esfandiari’s team, Manju Sharma, is a biologist, and while extracting exosomes from patient samples and examining the RNA profile, she is simultaneously training the other students in cell cultures and ensuring the procedures are followed correctly and safely.

The next five years, Esfandiari and her team will be working closely with extracellular vesicles and their impact on nerve regeneration. The lab’s advanced equipment, such as the ONI Nanoimager and the Fluidnatek LE-50 Electrospinner, allows the team to mimic the human body’s electric field and analyze the functional importance of vesicles, which could result in significant advancements in regenerative medicine.

“One thing I love about science is that you can use your knowledge and combine it with creativity and imagination to come up with some new ideas,” Esfandiari said. “The NIH recognized our creativity and gave us the opportunity to explore our unique concepts, which is highly important to me as a scientist with an imaginative mind.”

Source – University of Cincinnati