Grant boosts UF’s stem cell rescue mission

Faced with an adventure as familiar as the movies but with real public health issues at stake, scientists at Dennis Steindler’s lab at the University of Florida’s McKnight Brain Institute have received $1.3 million from the National Institutes of Health to continue work to understand how adult stem cells may be used to rescue injured areas of the brain.

In this true-to-life drama, the victims are brain cells stricken by physical injury or disease. Somehow, these imperiled cells call for help. The would-be heroes are stem cells that mysteriously hear the cries and track down the injured cells.

The scenario is common to an array of neurological disorders in which damaged cells signal they need help and repair is attempted, including traumatic brain injury, stroke, Parkinson’s disease, multiple sclerosis and Alzheimer’s disease, said Steindler, Ph.D., a researcher in the Program of Stem Cell Biology at the UF College of Medicine. But existing stem cells in the brain or elsewhere in the body don’t respond in sufficient time or number to save the day.

“The ultimate goal of this work is to have an injured brain that is able to beckon stem cells from anywhere in the body to come to the place where the injury is and help fix it,” said Steindler, a neuroscience professor. “If our indigenous population of stem cells in brain marrow were enough to do the job, and the homing molecules that were secreted by the injury sites were enough, we wouldn’t have this work to do. Obviously they are not enough, so we have to prop up the system.”

Neurological disorders affect an estimated 50 million Americans each year, according to the National Institute of Neurological Disorders and Stroke.

Thus far, UF scientists have identified the rescuers — neural stem cells that exist in spongy tissue called brain marrow, as well as stem cells that exist in bone marrow. Now, with the latest NIH funding, scientists will use rodent models to delve into the homing factors that call stem cells to the region of the injured brain, and they will try to unravel the differentiation factors that enable stem cells to morph into functional brain cells.

Research by UF colleagues Eric Laywell, Ph.D., and Tong Zheng, Ph.D., confirms that when different types of stem cells are introduced to the fluid-filled spaces in the brain marrow, the stem cells home in on special areas of the brain where new neurons are routinely generated, Steindler said.

It’s certain that injured tissues beckon stem cells to come to them through a homing process, Steindler said. Of particular interest is a gene associated with immune system regulation called SDF1, a homing factor that also is being studied by other members of UF’s multidisciplinary stem cell research team, including Edward Scott, Ph.D., Maria Grant, M.D., and Bryon Petersen, Ph.D.

“We know SDF1 is in the brain,” Steindler said. “Now, we’re going to learn if it acts in the brain as it does in the liver, eye and blood, as the other three labs are studying. We believe it’s one (homing) factor that’s naturally present in injured tissues, and we’re going to try to enhance it.”

In the meantime, UF scientists Katrin Goetz, Ph.D., and Bjorn Scheffler, Ph.D., have concentrated on growth factors and extracellular matrix molecules that enable stem cells to literally set up shop and effect repairs at an injury site — the differentiation factors. Their work dovetails with the stem cell plasticity studies conducted by Naohiro Terada, M.D., Ph.D., also a member of the Program of Stem Cell Biology and an associate professor of pathology, immunology and laboratory medicine.

“Together, they (Laywell and Zheng) found there is an endogenous homing mechanism in brain marrow, and that’s extremely important to this project,” Steindler said. “Dr. Goetz and Dr. Scheffler have been figuring out the ways in which we can differentiate stem cells and turn them into the cells we want. Understanding those differentiation mechanisms of turning stem cells into adult neurons likewise is crucial.”

Steindler believes the stem cell therapies that initially come into use will likely involve cells derived from a donor or a culture dish that are introduced to the area where they’re needed, he said. The next generation therapy Steindler calls the “home run” treatment, in which cells within the body are “taught and mobilized.”

“The home runs you will be hearing about will be about the body healing itself,” Steindler said.