Stem Cells from Jaw Bone Help
Repair Damaged Cartilage
NEW YORK , NY (Oct. 10, 2016)–Columbia
College of Dental Medicine researchers have identified stem cells that can make
new cartilage and repair damaged joints.
Repair Damaged Cartilage
The cells reside within the temporomandibular joint (TMJ), which
articulates the jaw bone to the skull. When the stem cells were manipulated in
animals with TMJ degeneration, the cells repaired cartilage in the joint. A
single cell transplanted in a mouse spontaneously generated cartilage and bone
and even began to form a bone marrow niche.
The findings were published on Oct. 10 in Nature Communications.
“This is very exciting for the field because patients who have
problems with their jaws and TMJs are very limited in terms of clinical
treatments available,” said Mildred C. Embree, DMD, PhD, assistant professor of
dental medicine at Columbia
and the lead author of the study. Dr. Embree’s team, the TMJ Biology and
Regenerative Medicine Lab, conducted the research with colleagues including
Jeremy Mao, DDS, PhD, the Edwin S. Robinson Professor of Dentistry (in
Orthopedic Surgery) at Columbia .
Up to 10 million people in the United States , primarily women,
have TMJ disorders, according to the National Institutes of Health. Options for
treatment currently include either surgery or palliative care, which addresses
symptoms but can’t regenerate the damaged tissue. Dr. Embree’s findings suggest
that stem cells already present in the joint could be manipulated to repair it.
Cartilage helps to cushion the joints and allows them to move
smoothly. The type of cartilage within the TMJ is fibrocartilage, which is also
found in the knee meniscus and in the discs between the vertebrae. Because
fibrocartilage cannot regrow or heal, injury or disease that damages this
tissue can lead to permanent disability.
Medical researchers have been working to use stem cells,
immature cells that can develop into various types of tissue, to regenerate
cartilage. Given the challenges of transplanting donor stem cells, such as the
possibility of rejection by the recipient, researchers are especially
interested in finding ways to use stem cells already living in the body.
“The implications of these findings are broad,” said Dr. Mao,
“including for clinical therapies. They suggest that molecular signals that
govern stem cells may have therapeutic applications for cartilage and bone
regeneration. Cartilage and certain bone defects are notoriously difficult to
heal.” Dr. Mao is co-director of the Center for Craniofacial Regeneration at Columbia . His own
research with stem cells has regenerated teeth and the meniscus, the pad of
cartilage within the knee joint, and the TMJ in 2003.
In a series of experiments described in the new report, Dr.
Embree, Dr. Mao, and their colleagues isolated fibrocartilage stem cells
(FCSCs) from the joint and showed that the cells can form cartilage and bone,
both in the laboratory and when implanted into animals. “I didn’t have to add
any reagents to the cells,” Dr. Embree said. “They were programmed to do this.”
And while some approaches to regenerating injured tissue require growth factors
or biomaterials for the cells to grow on, she noted, the FCSCs grew and matured
spontaneously.
Dr. Embree and her team also identified a molecular signal, Wnt,
that depletes FCSCs and causes cartilage degeneration. Injecting a Wnt-blocking
molecule called sclerostin into degenerated TMJs in animals stimulated
cartilage growth and healing of the joint.
She and her colleagues are now searching for other small
molecules that could be used to inhibit Wnt and promote FCSC growth. The idea,
according to Dr. Embree, will be to find a drug with minimal side effects that
could be injected right into the joint.
Children with juvenile idiopathic arthritis can have stunted jaw
growth that can’t be treated with existing drugs, Dr. Embree noted. Since the
TMJ is a growth center for the jaw, the new research may offer strategies for
treating these children and lead to a better understanding of how the jaw
grows and develops. While orthodontists currently rely on clunky technologies
like headgear to modify jaw growth, she added, the findings could point toward
ways to modulate growth on the cellular level.
Ultimately, Dr. Embree and her team say, the findings could lead
to strategies for repairing fibrocartilage in other joints, including the knees
and vertebral discs. “Those types of cartilage have different cellular
constituents, so we would have to really investigate the molecular
underpinnings regarding how these cells are regulated,” the researcher said.
The
study is titled, “Exploiting endogenous fibrocartilage stem cells to regenerate
cartilage and repair joint injury.”
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