James Cronk

James Cronk is a researcher in the University of Virginia’s Medical Scientist Training Program.

CHARLOTTESVILLE, Va. — A University of Virginia neuroscience lab may have discovered how to load immune cells into the brain to battle neurodegenerative diseases without the need for radiation.

The researchers were able to send macrophages — large immune cells that target and destroy infections — into the brains of mice, a feat previously believed impossible without radiation. Further, they determined that macrophages remain a unique cell type once introduced into the brain, and now have a gene signature that can be used to track cells in the brains of humans and animals.

“We know there are certain diseases where getting macrophages in the brain is beneficial,” said James Cronk, a researcher in UVa’s Medical Scientist Training Program. “This study helps on both ends because it helps see how we might get macrophages in the brain when needed and get them out when they’re harmful.”

Cronk’s team bred mice to remove microglia, a different type of immune cell prevalent in the brain, creating a “niche” to introduce other cells. Through bone marrow transplants, they could see that macrophages filled that void and retained a unique genetic makeup.

Further, Cronk said, the macrophages retained a healing signature and did not cause any negative effects on brain function.

“That was super cool,” Cronk said. “As soon as we realized the cells were engrafting without the need for irradiating, we knew we were on to something.”

The treatment, if tested further and approved for human use, could be especially helpful for pediatric diseases, when doctors are wary of irradiating a child’s head. Cronk finished his doctorate in 2016 and will graduate from medical school in May. After that, he will begin a residency training in pediatrics at Johns Hopkins Hospital.

The next step in the research, Cronk said, whether at UVa or at Johns Hopkins, is to understand whether macrophages are already present in neurodegenerative diseases, and whether they serve a positive or negative purpose.

The research, published Wednesday in the Journal of Experimental Medicine, also required work from computational biologists and bioengineers. The project is an example of growing collaboration between UVa’s Department of Neuroscience and the School of Engineering & Applied Sciences, said Jonathan Kipnis, chairman of the Department of Neuroscience and director of the Center for Brain Immunology and Glia.

“In today’s world, there is no such thing as an individual science career,” Kipnis said. “To compete, you have to collaborate with your peers.”

The development of the gene signature is now publicly available data, Kipnis said, and, while Cronk is leaving, the lab will carry on the work and push it further.

“These lab mice live only two years; humans live 80 years,” Kipnis said. “So, we introduce these cells in their brains, but we don’t know what might happen in our lives that will let one cell get into ours.”

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Ruth Serven is a reporter for The Daily Progress. Contact her at (434) 978-7254, rserven@dailyprogress.com or @RuthServen on Twitter.

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