Jefferson Researchers Receive $1.7 Million Grant to Study Stem Cells in Intervertebral Discs of the Spine
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.”
Media Only Contact:
Richard Cushman
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 6/4/2009