PDGF-BB Protein Therapy Targets Pericytes to Encourage Nerve Regrowth
Researchers here report on a novel approach to encourage nerve regeneration, and demonstrate positive results in mice with spinal cord injury. Delivering platelet-derived growth factor BB (PDGF-BB) as a protein therapy to the injured nerve tissue changes the behavior of pericyte cells that normally interfere in any possible regrowth of the axons making up the nerve. In the presence of PDFG-BB, pericytes act to indirectly encourage axon regrowth. As the researchers note, this discovery likely has other applications beyond treating spinal cord injuries.
Spinal cord injuries are severe not only because they prevent transmission of information across the site of the injury, but because all of the vasculature structure and function is also compromised. Previous research suggesting pericytes interfere with spinal cord injury recovery had led some scientists to recommend clearing them from the lesion site to aid repair. But cancer research has indicated pericytes' properties change when they're exposed to a protein called platelet-derived growth factor BB (PDGF-BB), and the cells act to encourage blood vessel formation. This is one way tumors generate their own blood supply.
Earlier neuroscience research also indicated that pericytes are highly "plastic," meaning they are very responsive to changes in the microenvironment - including the presence of PDGF-BB. Researchers saw potential to harness that cell-protein relationship to stabilize the vasculature surrounding a spinal cord injury. In the process, they found the newly sprouted blood vessels established a pathway for regenerated axons to follow.
Turning to experiments in animals with spinal cord injury, researchers waited for seven days after the injury - the equivalent of about nine months in a human adult - before injecting a single dose of PDGF-BB at the injury site. Analysis of tissue four weeks after the injury showed that the PDGF-BB injection produced robust axon regenerative growth compared to the axon response in injured control mice. Electrophysiological and movement assessments of injured animals treated with PDGF-BB detected sensory activity beyond the lesion site and showed the mice regained better control of their hind limbs compared to control mice. The animals also were less sensitive to a non-painful stimulus, suggesting they did not experience the neuropathic pain that is often triggered by a spinal cord injury.
Link: https://news.osu.edu/building-cellular-bridges-for-spinal-cord-repair-after-injury/