Growth Factor Therapy Alters Cells that Prevent Spinal Cord Repair
COLUMBUS, Ohio – Scientists at The Ohio State University College of Medicine have discovered that cells in the spinal cord that prevent regeneration after a spinal cord injury (SCI) can be manipulated, through gene therapy, to become increasingly supportive of repair.
The study, published yesterday (10/18) in the Journal of Neuroscience, shows that treating an injured adult spinal cord, by genetic delivery of a high-level growth factor found in the developing brain, can change the behavior of glial scar cells called astrocytes.
Astrocytes are cells found throughout the brain and spinal cord that normally support the nerve cells and keep them healthy. When an injury occurs, they protect the neurons by forming a scar that walls off the injury, but this wall prevents repair as the nerve fibers, called axons, try to re-grow.
“We were successful in driving the astrocytes to becoming a much better growth-promoting cell type after the injury,” says Lyn Jakeman, associate professor of physiology and cellular biology and senior author of the study.
Robin White, a graduate student in Ohio State’s interdisciplinary Neuroscience Graduate Studies Program from Jakeman’s lab, tested whether increasing levels of the transforming factor could cause astrocytes to elongate and provide supportive structures for growing axons. The key to this idea was new evidence that immature astrocytes are present in adult mice after injury, and that these immature cells closely resemble cells that support growth in most regenerating systems.
“Astrocytes are a wonderful target for spinal cord repair because they have potential to be either detrimental or supportive of growing axons. Our idea was to try to target the very young astrocytes that are already at the site of injury to be supportive of regeneration” says White, who is also the study’s first author.
According to Jakeman and her team, although the research shows promise for regeneration in mice, there still remain limitations to growth of injured adult animal axons. However, they say, strategies directed toward modification of the astrocyte response soon after a spinal cord injury represents a first step in the right direction for damaged tissue repair after SCI.
“It is our hope that we can learn how the programs and signaling pathways in these existing immature cells are controlled so that we can use them to make bridges for regeneration in patients with spinal cord injury,” Jakeman adds.
Along with Jakeman and White, other Ohio State researchers involved in the study were John Gensel, Dana McTigue and Brian Kaspar. Meghan Rao, from the Research Institute at Nationwide Children’s Hospital, also participated in the research.
Funding from the NIH’s National Institute for Neurological Disorders and Stroke, along with grants received from Ohio State’s College of Medicine, supported this research.