Researchers led by the University of Pennsylvania School of Medicine (Penn Medicine) may have found a way to press pause on spinal disc injuries, offering doctors more time to treat them before worse issues develop. The preclinical researchers found that the cells in the outer region of spinal discs become stressed and kick off a subpar healing process after injuries, which researchers then found can temporarily be blocked with drugs that calm the cells down. The study was conducted using specially engineered biomaterials and small animal models.
The Preclinical Study
Published in Nature Biomedical Engineering, this preclinical study (e.g. on animals) sheds some light on the challenges facing disc degeneration and associated back pain. The researchers are now looking at the whole disc in order to identify new therapy targets.
For example, discs are pressurized and structured similarly like water balloons, with water-attracting proteins in the inner portion restrained by an outer layer of fibrous tissue containing cells that are under a constant stretch. The discs are designed to cushion the vertebrae from directly and painfully contracting each other. The researchers from Penn-Medicine and McKay Lab sought to focus their research on the often overlooked outer region discs.
Researchers have seen that when an injury like a slipped disc occurs and pressure is lost, the suddenly released tissue becomes disorganized. Upon study in small animal models, the research team found it results in the generation of repair tissue that doesn’t resemble the normal tissue but rather scar tissue.
Moreover, they found that programmed cell death (apoptosis) occurs rapidly—within 24 hours of the injury. This represents a big problem as cells in the discs lack a blood supply and cannot easily repopulate with the new cells needed for regeneration.
The team found that using a biological inhibitor of cell contraction, such as fasudil, could effectively “relax” the cells from the shock of suddenly losing their typical stretched state. As they relax, the cells delay their default healing response, which has the potential to buy doctors what is called a “therapeutic window” to intervene. A note fasudil has been approved in China and Japan but not in the U.S. or Europe.
The research is revealing that the treatment of disc injuries immediately after injury is critically important—prior to the transition in phenotype occurs and scar tissue forms. Inhibitors, such as fasudil applied systematically or in combination with surgical implementation of biomaterials, that are designed to restore native tissue could be a future treatment.
- National Institutes of Health
- Department of Veterans Affairs
- The Ministry of Science and Technology, Taiwan
- The National Health Research Institute
- The National Science Foundation’s Science and Technology Center for Engineering and Mechanobiology
Edward Bonnevie, PhD, Penn Medicine’s McKay Orthopedic Research Laboratory
Robert L Mauck, PhD, professor of Orthopedic Surgery, director McKay Lab