DURHAM, N.C.-- Duke researchers may have found a
promising stem cell therapy for preventing osteoarthritis after a joint
injury.
Injuring a joint greatly raises the odds of
getting a form of osteoarthritis called post-traumatic arthritis, or PTA. There
are no therapies yet that modify or slow the progression of arthritis after
injury.
Researchers at Duke University Health System
have found a very promising therapeutic approach to PTA using a type of stem
cell, called mesenchymal
stem cells (MSCs), in mice with fractures that typically would lead to
them developing arthritis. Their findings could lead to a therapy that would be
used after joint injury and before signs of significant osteoarthritis.
The scientists thought the stem cells would work
to prevent PTA by altering the balance of inflammation and regeneration in knee
joints, because these stem cells have beneficial properties in other regions of
the body.
"The stem cells were able to prevent
post-traumatic arthritis," said Farshid Guilak, Ph.D., director of orthopaedic
research at Duke and senior author of the study.
The study was published on August 10 in Cell Transplantation.
The researchers also thought that a type of mice
bred for their super-healing properties would probably fare better than typical
mice, but they were wrong.
"We decided to investigate two therapies for the
study, said lead author Brian Diekman, Ph.D., a postdoctoral researcher in the
Guilak lab. "We thought that stem cells from so-called superhealer mice would be
superior at providing protection, and instead, we found that they were no better
than stem cells from typical mice. We thought that maybe it would take stem
cells from superhealers to gain an effect as strong as preventing arthritis
after a fracture, but we were surprised – and excited – to learn that regular
stem cells work just as well."
Certain people appear to fall into the
superhealer category, too. They bounce back quickly and heal well naturally
after a fracture, while other people eventually form cases of arthritis at the
fractured joint, said Guilak, who is a professor of orthopaedic surgery and
biomedical engineering.
"The ability of the superhealer mice to have
superior healing after a fracture may go beyond the properties of their stem
cells and be some beneficial factor, like a growth factor, that we don't know
about yet," Guilak said.
The delivery of 10,000 typical or superhealer
stem cells to the joint prevented the mice from developing PTA, unlike a control
group that received only saline.
Diekman said the team looked at markers of
inflammation and saw that the stem cells affected the inflammatory environment
of the joint after fracture.
"The stem cells changed the levels of certain
immune factors, called cytokines, and altered the bone healing response," said
Diekman, who is also with the Duke Department of Biomedical Engineering.
Guilak said that very few studies have purified
stem cells to the degree they were purified for this study. They used
mesenchymal stem cells, which are bone marrow cells not destined to become part
of blood.
Diekman said that one of the challenges in the
field is isolating and developing a system for sorting the specific cells they
wanted, the mesenchymal stem cells, which form a very rare cell type in the bone
marrow.
"We found that by placing the stem cells into
low-oxygen conditions, they would grow more rapidly in culture so that we could
deliver enough of them to make a difference therapeutically," Diekman said.
Funding came from the Arthritis Foundation and
NIH grant AR50245.
Other authors include Craig R. Louer, Bridgette
D. Furman and Steven A. Olson of the Duke Department of Orthopedic Surgery;
Chia-Lung Wu of Orthopedic Surgery and the Department of Biomedical Engineering;
and Janet L. Huebner and Virginia B. Kraus of the Duke Department of
Medicine.
