Mesenchymal stem cell injections represent cutting edge of OA intervention
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Intra-articular injections of mesenchymal stem cells into the synovium may yield expression of a number of genes that inhibit progression of osteoarthritis, according to a speaker at the 2021 OARSI World Congress virtual meeting.
Ichiro Sekiya, MD, PhD, of Tokyo Medical and Dental University in Tokyo, Japan, explained the rationale for this treatment approach. “Synovial MSCs have a high chondrogenic potential,” he said in his presentation. “Synovium itself has a high regenerative potential.”
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In early work, Sekiya’s group collected bone marrow, synovium, periosteum, adipose tissue and skeletal muscle from individuals who underwent anterior cruciate ligament reconstruction. They observed that after enzyme digestion, synovial cells proliferate and form colonies. Approximately 50 million synovial mesenchymal stem cells can be harvested in 2 weeks, according to Sekiya. “These are used for cell therapy,” he said.
In pre-clinical studies, injection of human MSCs into the knees of rats inhibited cartilage degeneration and progression of OA. Genetic analysis showed that intraarticular expression of proteoglycan-4 (PRG4), bone morphogenetic protein-2 (BMP-2), BMP-6 and TNF-stimulated gene-6 (TSG-6) were significantly increased after injections.
Sekiya explained the possible mode of action of this treatment modality and why these genes are important. “Synovial MSCs injected into the knee joint mostly migrated to the synovium and act as anti-inflammatory agent through TSG-6 expression, as a lubrication agent through PRG-4 expression and incur cartilage matrix synthesis by BMP-6 expression,” he said. “Consequently, exogenous MSCs can inhibit progression of OA.”
Among 14 clinical reports from other groups documenting this approach, improvements in pain parameters have been reported in “all studies,” according to Sekiya. In addition, there have been no reports of fibrous synovium.
The most current data from Sekiya’s group is a prospective study of MSC injections in eight individuals with OA. The primary outcome was to assess how many patients would show an improvement in the projected cartilage area ratio — defined as an improvement in thickness greater than 1.5 mm — at the femoral posteromedial region from 30 weeks before to 30 weeks after synovial MSC injections. Two injections were given 15 weeks apart. “We only included patients who had cartilage loss immediately prior to injection,” he said.
Results showed that after the first injection, seven patients achieved the primary endpoint. “Most patients showed no further improvement beyond the effects of the first injection,” Sekiya said. “A second injection might not be necessary in a 30-week period.”
The adverse event profile showed that most patients had knee pain for a week immediately after injection. Itching in the hands 1 week after the first injection also occurred.
“Fully automated 3D MRI analysis showed that synovial MSC injections suppressed cartilage loss in patients with progressive OA,” Sekiya concluded.
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Sekiya I. Intraarticular Injections of Mesenchymal Stem Cells in Knee Osteoarthritis. Presented at: OARSI 2021 World Congress on Osteoarthritis; April 29-May 1 (virtual meeting).
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