Stem cell strategy for repairing joint damage shows promise in pig model
A method to turn human stem cells into cartilage cells showed promise for repairing damaged joint tissue in a pig model of knee cartilage injury. The findings, funded in part by NIA and published in Regenerative Medicine, provide a potential new therapeutic strategy that may help repair damaged cartilage and prevent osteoarthritis.
Articular cartilage is the tissue that covers the end of bone in joints. It helps prevent friction between bones and acts as a shock absorber during regular physical activities. Both acute injuries and everyday wear and tear can cause the cartilage to break down. If the loss of cartilage is severe, the underlying bone begins to break down, which leads to osteoarthritis.
Traditionally, damaged joint tissue is repaired with a technique called microfracture, for which surgeons create a small passageway that connects the bone marrow to the site of injury. This allows cells from the bone marrow to move to the damaged area. Once there, the cells produce new cartilage. But this procedure has drawbacks in that it requires two complicated surgeries and the repaired tissue is less durable.
In a new study, an international team of researchers refined a stem cell-based procedure that produces longer-lasting, higher-quality cartilage. The approach may also be easier to use in the clinic. The team included scientists from the University of California, Los Angeles; University of Southern California, Los Angeles; Nanjing Medical University, China; Sichuan University, China; Southeast University, China; University of Tübingen, Germany; and University of Guelph, Canada.
The researchers needed to test their ideas before trying the procedure in a clinic. For this test, they used a breed of miniature pig that is often used to try out potential therapies. They modified stem cells and implanted them into experimentally damaged knees, which led to integration of the implanted stem cells and repair of the damaged cartilage. After six months, the repaired tissue had all of the physical and molecular characteristics of undamaged cartilage. The tissue even got thicker and more compressible — qualities that help cartilage to cushion the joints. The study also found that the injected cells caused the pig’s own body to start making cartilage cells to further help in damage repair.
Additionally, in an important step toward translating this procedure into the clinic, the scientists developed a liquid in which the injectable cartilage cells can be frozen and later revived. This means that the therapeutic cells could be transported to clinics and stored for an extended period, which would be ideal, should future research show the technology is safe and effective in humans.
The authors noted that although the implanted cartilage cells did not cause an immune reaction in the pigs, that might happen in humans. The scientists recommend that if this technology translates to the clinic, health care providers should screen patients carefully to determine who may have an immune reaction. Additionally, the authors note that future studies will determine whether the successful repair of the cartilage reduces joint pain. Still, overall, the new technique is a significant step toward better therapies for joints with damaged cartilage.
This research was supported in part by NIA (R01AG058624) and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR071734).
Reference: Petrigliano FA, et al. Long-term repair of porcine articular cartilage using cryopreservable, clinically compatible human embryonic stem cell-derived chondrocytes. NPJ Regenerative Medicine. 2021;77(6). doi: 10.1038/s41536-021-00187-3.