Knee osteoarthritis (OA) is a long-term condition that affects millions of people worldwide. It occurs when the cartilage in the knee begins to break down, often due to aging, injury, or repeated stress on the joint. Early signs of OA include swelling, stiffness, and pain in the knee. Over time, the condition worsens, leading to a narrowing of the space between bones, the development of bony growths (osteophytes), and reduced joint mobility. This progression can significantly impact a person’s quality of life, especially in older adults.
One of the major challenges in treating knee OA is the poor ability of cartilage to repair itself. Cartilage lacks blood vessels and relies on nearby joint fluid and surrounding tissues for nutrients, making it especially vulnerable to damage. As a result, finding effective ways to heal or regenerate damaged cartilage has been a major focus of research in recent years.
In this review, Zhang et al. summarize the basic research and clinical studies to promote inflammatory chondrogenesis in the treatment of OA and provide a theoretical basis for clinical treatment.
The Role of Stem Cells in Cartilage Repair
Researchers have explored several treatment options for OA, including injections of corticosteroids, platelet-rich plasma, sodium hyaluronate, and more recently, stem cells. Among the various stem cell types being studied, human umbilical cord mesenchymal stem cells (HUC-MSCs) have shown promising results.
HUC-MSCs are a type of stem cell collected from the umbilical cords of newborns. These cells are especially attractive for medical use because they are easy to obtain, do not cause pain or harm to the donor, and are free from the ethical concerns that sometimes surround embryonic stem cells. They have also demonstrated the ability to multiply, change into different cell types (including cartilage cells), and regulate inflammation in the body.
Biological Benefits of HUC-MSCs in OA Treatment
According to the authors, what sets HUC-MSCs apart is their ability to both repair cartilage and control the inflammatory processes that worsen OA. These cells release helpful substances like cytokines, growth factors, and extracellular vesicles that support cartilage repair and reduce joint inflammation. HUC-MSCs can also develop into chondrocytes – cells that produce and maintain healthy cartilage.
In studies comparing HUC-MSCs to bone marrow-derived stem cells, HUC-MSCs have shown a higher potential for cartilage formation and a lower tendency to become fat or bone cells. These qualities make them a strong candidate for regenerating joint cartilage in OA patients. Additionally, the extracellular matrix (ECM) they produce is rich in type II collagen, which is essential for building strong, healthy cartilage.
Another biological benefit of HUC-MSCs is their ability to function well in low-oxygen environments, such as the interior of a joint. This makes them well suited for surviving and thriving in the harsh conditions of damaged knee joints. They also produce anti-inflammatory proteins like IL-10 and TGF-β1, which help reduce pain and inflammation, making the joint environment more suitable for healing.
Clinical Use of HUC-MSCs and Evidence of Effectiveness
Over the past decade, HUC-MSCs have been tested in laboratory studies, animal models, and human clinical trials. Results consistently show that these cells can improve symptoms, protect joint structures, and possibly slow the progression of OA.
In animal models of OA, researchers found that injecting HUC-MSCs into the knee joint helped reduce cartilage breakdown and cell death. In these studies, both single and repeated injections produced similar benefits, including better cartilage matrix production and less joint degeneration.
In human trials, HUC-MSCs have been tested in patients with moderate to severe OA. Results show improved joint function, reduced pain, and even signs of new cartilage formation on imaging studies. When compared to traditional treatments like sodium hyaluronate injections, HUC-MSC therapy has been shown to offer faster, longer-lasting relief and more meaningful improvements in joint health.
Additionally, treatment with HUC-MSCs has proven to be well tolerated and safe, with no serious side effects reported. Minor discomfort after the injection was typically short-lived and did not require medical intervention.
Mechanisms of Action and How HUC-MSCs Promote Healing
Zhang et al. found that HUC-MSCs help reduce the harmful effects of OA in several ways. First, they lower levels of inflammatory molecules like IL-1β, TNF-α, and IL-6 that are commonly found in arthritic joints. These substances are responsible for breaking down cartilage and increasing pain. HUC-MSCs also block enzymes such as MMP-13 and ADAMTS-5, which are known to degrade the cartilage structure.
At the same time, HUC-MSCs boost the production of cartilage-supporting proteins like collagen type II, aggrecan, and SOX9. These proteins are critical for rebuilding and maintaining the smooth, elastic tissue that cushions the ends of bones in the joint.
In addition to their anti-inflammatory and regenerative properties, HUC-MSCs influence the immune system by shifting inflammatory cells from a damaging state to a healing state. This shift helps calm the immune response within the joint and supports the repair process.
Several key cell signaling pathways – such as PI3K/Akt, mTOR, and Notch – are involved in this regenerative process. These pathways help control cell survival, growth, and the formation of new cartilage. As researchers continue to uncover how these pathways work, the authors anticipate new possibilities for targeted therapies will emerge.
Advantages Over Traditional and Other Stem Cell Treatments
Compared to other types of stem cells, such as those taken from bone marrow or fat tissue, HUC-MSCs offer multiple advantages. They are more readily available, easier to collect, and carry less risk of causing an unwanted immune response. They also multiply faster, have a greater capacity to form cartilage, and are less likely to develop into bone or fat cells – features that are particularly important when the goal is to repair joint cartilage.
Unlike treatments that simply reduce symptoms, such as painkillers or steroid injections, HUC-MSC therapy has the potential to address the root cause of OA by rebuilding damaged cartilage and rebalancing the joint’s internal environment.
Because of these advantages, the authors believe HUC-MSCs may represent a major step forward in the treatment of OA, especially for patients who have not responded well to traditional therapies or who are looking for a regenerative option before considering surgery.
A Promising Path Forward for Osteoarthritis Care
Human umbilical cord mesenchymal stem cells offer a new and exciting option for patients with knee osteoarthritis. With their ability to reduce inflammation, promote cartilage repair, and restore joint function, HUC-MSCs are rapidly becoming an important focus in regenerative medicine. As more research is conducted and the science behind these cells becomes clearer, they may soon become a standard part of OA treatment, offering hope for millions of people living with joint pain and stiffness.
Zhang P, Dong B, Yuan P, Li X. Human umbilical cord mesenchymal stem cells promoting knee joint chondrogenesis for the treatment of knee osteoarthritis: a systematic review. J Orthop Surg Res. 2023 Aug 29;18(1):639. doi: 10.1186/s13018-023-04131-7. PMID: 37644595; PMCID: PMC10466768.
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