Engineer Wins $2.24 Million NIH Grant to Develop a Cell-Free Stroke Therapy

That’s the vision behind a new $2.24 million study led by Yan Li, the Simon Ostrach Professor of Engineering and Professor of Chemical and Biomedical Engineering at the FAMU-FSU College of Engineering. The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), is funding the work.

Li is teaming up with the National High Magnetic Field Laboratory and the Florida State University College of Medicine to reimagine recovery from stroke and other neurological disorders.

“We are engineering and bio-manufacturing human stem-cell-derived microglia extracellular vesicles to treat ischemic stroke,” said Li, lead researcher for the project.

What are microglia and extracellular vesicles?

Microglia and extracellular vesicles (EVs) work together like specialized teams of cells and their mail carriers. Think of microglia as permanent resident workers and EVs as a package-delivery network that cells use to send messages. Lab-grown microglia naturally release EVs, microscopic packages that ferry proteins, fats and microRNAs to neighboring cells.

That cargo can calm inflammation and encourage regrowth, which may change how the brain recovers from a stroke.

“The human stem cell-derived microglia extracellular vesicles contain therapeutic protein and microRNA cargo to treat stroke,” Li said. “They also can cross blood-brain barriers and have low immunogenicity. Their natural capacity to promote repair and restore balance could transform how we treat some of the most challenging diseases.”

How does Li’s team grow brain immune cells in the lab?

Microglia, the brain’s resident immune cells, play a crucial role in maintaining healthy brain tissue. There are two types: M1, which promotes inflammation and can worsen injuries, and M2, which soothes inflammation and supports tissue repair. The key to Li’s approach lies in harnessing the restorative powers of the M2 state.

Extracting microglia from human brains is a daunting task. Instead, Li’s team reprograms ordinary adult skin or blood cells into stem cells, then coaxes those stem cells into becoming microglia-like cells in the lab. The result is a renewable supply of M2 microglia, primed to deliver help where it’s needed most.

Why does this research matter for stroke patients?

Every year, ischemic stroke strikes without warning, often taking away a person’s speech, movement or independence. Current treatments are limited, and many survivors face a long, uncertain road back. Li’s team is harnessing the body’s own healing signals, packaged in these tiny vesicles, to tip the odds in favor of recovery.

After a stroke, the brain’s immune response can help or harm. The team is designing vesicles that turn down inflammation and turn up repair.

How will the researchers test the vesicles?

The next step is to produce these vesicles at scale and put them to the test. Li’s lab, with partners at the FSU College of Medicine and the National High Magnetic Field Laboratory, will study their effects on 3D brain organoids, miniature models of human brain tissue used to evaluate stroke injury and repair.

The researchers will observe how the EVs affect the organoid environment. Do they reduce inflammation? Do they promote neuronal regrowth? The answers could point toward a cell-free stroke therapy that draws on the body’s natural repair mechanisms without the risks of transplanting living cells.

What is the long-term goal of the project?

“The ultimate goal of this research is to develop cell-free therapeutics for translational stroke treatment,” Li said.

If the work succeeds, the team could turn laboratory discoveries into practical medicine that helps stroke survivors recover.

Source – FAMU-FSU