(PHILADELPHIA) Scientists at Jefferson Medical College have received a five-year, $1.7 million National Institutes of Health grant funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases to study mechanisms regulating stem cell self-renewal and differentiation with the aim of regenerating diseased and painful intervertebral discs. A previous study by the same group showed that stem cells exist in both animal and human intervertebral discs. This grant will enable the researchers to continue studying the disc cells and determine factors which govern their activities in health and disease.
"Disc degeneration and the associated back pain that goes with it costs the U.S. healthcare industry approximately $100 billion annually," said Irving M. Shapiro, Ph.D., associate director of Orthopedic Research and the director of the Cell and Tissue Engineering Graduate Program at Jefferson Medical College of Thomas Jefferson
University. "As a major cause of lost productivity worldwide it is critical that we develop a treatment that will regenerate intervertebral disc structure and function."
A variety of factors contribute to the degeneration of the intervertebral disc including age, genetics and biomechanical factors. Several surgical procedures are available to pacify the pain associated with the degenerative disc, but the most common procedures often only provide symptomatic relief. No current therapy can completely restore the function of a degenerated disc nor prevent its further deterioration. Historically, investigations of the intervertebral disc have been limited in scope, leading to a lack of understanding of the biology and function of both healthy and diseased tissues.
"Researchers have tried repairing the discs by injecting them with agents that are thought to have beneficial effects on cell function," said Makarand Risbud, Ph.D, associate professor of Orthopedic Surgery at Jefferson Medical College of Thomas Jefferson University. "However, these treatments are limited in their effectiveness in restoring disc structure and function. Our ongoing studies suggest that a group of proteins that compromise the notch signaling pathway in the intervertebral discs are central to this process. These proteins regulate a variety of activities of stem cells including proliferation, self-renewal and differentiation. Our goal is to harness the body's own regenerative potential and activate endogenous cells."
Drs. Risbud and Shapiro are collaborating with Drs. Todd Albert and D. Greg Anderson, their clinical colleagues at the Rothman Institute at Jefferson, as well as Dr. Ernestina Schipani, an expert in molecular genetics at Harvard University. The investigators plan to develop a genetically engineered mouse model that lacks selected proteins of the notch signaling pathway in the intervertebral disc. This model will provide important mechanistic insights into the role of the notch signaling pathway in controlling disc cell activities.
"Eventually, we hope to be able to regulate the activities of the disc cells including fostering their inherent regenerative potential," said Risbud. "If we are able to do this it could lead to development of new therapies to treat degenerative disc disease providing relief to millions of back pain suffers."
|Contact: Rick Cushman|
Thomas Jefferson University