Exploring New Options for Knee Osteoarthritis
Knee osteoarthritis is a common joint condition that develops as cartilage and other tissues within the knee gradually change over time. For many people, this can lead to ongoing pain, stiffness, and difficulty staying active.
As regenerative medicine continues to advance, researchers are studying whether mesenchymal stem cells (MSCs) may offer another way to support joint health and improve symptoms.
A 2025 Phase I clinical trial investigated a particularly interesting source: human placenta-derived MSCs. Researchers evaluated whether multiple injections of these cells, combined with hyaluronic acid, could safely improve pain and function in people with moderate knee osteoarthritis.
A Closer Look at the Study
The clinical trial included 26 adults with stage II or III knee osteoarthritis.
Participants were divided into two treatment groups:
- 15 received placenta-derived MSCs combined with hyaluronic acid
- 11 received hyaluronic acid alone
Rather than testing just one treatment, researchers used three injections given four weeks apart. Participants were then followed for a full year.
Researchers measured pain, stiffness, and overall knee function using commonly used osteoarthritis assessments. MRI scans and blood testing were also used to look for changes within the joint and signs related to inflammation.
Encouraging Improvements in Pain and Function
The placenta-derived MSC group showed encouraging changes over the course of the study. At both six months and one year, participants receiving MSCs experienced significant improvements in measurements of knee pain and overall function compared with where they started.
Researchers used the WOMAC assessment, which measures pain, stiffness, and difficulty with everyday physical activities, as well as a separate pain scale. Both showed improvements in the MSC-treated group during the follow-up period.
Importantly, these improvements were still present at the one-year mark, suggesting that the benefits observed in the study were not limited to the first few weeks or months after treatment.
A Positive Safety Profile
Safety was an especially important part of this Phase I trial.
Researchers reported no serious adverse events associated with the three-injection treatment approach. Some participants experienced temporary discomfort such as knee pain, swelling, or stiffness following injections, but these effects resolved within several days.
Overall, the researchers concluded that repeated injections of placenta-derived MSCs combined with hyaluronic acid were well tolerated in the patients studied.
This is an encouraging finding because it provides additional human clinical evidence supporting the continued study of placenta-derived MSCs for joint-related conditions.
How Might Placenta-Derived MSCs Help?
MSCs are being researched for osteoarthritis because of the way they interact with the environment surrounding damaged or inflamed tissue.
Rather than simply replacing worn cartilage, MSCs can release biological signals that may help regulate inflammation and support the body’s natural repair processes.
The researchers found a significant reduction in interleukin-2 (IL-2) in the MSC group after six months. IL-2 is involved in immune and inflammatory activity, so this finding may provide another clue about how placenta-derived MSCs could influence the environment within the body.
MRI scans didn’t show significant changes in cartilage thickness during the study, meaning more research is needed to determine how these cells may affect the physical structure of the joint over time.
Why This Research Stands Out
One particularly interesting feature of this trial was its use of three consecutive placenta-derived MSC injections.
According to the researchers, relatively few clinical studies have explored repeated doses of placenta-derived MSCs for knee osteoarthritis. This makes the study an important addition to the growing research surrounding cell-based approaches for joint health.
The combination of a favorable safety profile and sustained improvements in pain and function at one year provides encouraging evidence for continued investigation.
Looking Ahead
This Phase I clinical trial highlights the growing potential of placenta-derived MSCs in regenerative joint research.
For patients with moderate knee osteoarthritis, three injections of placenta-derived MSCs combined with hyaluronic acid were well tolerated and were associated with meaningful improvements in pain and function that remained evident one year after treatment.
While larger and more controlled clinical trials are still needed, these results offer another promising step toward understanding how placenta-derived MSCs may help support joint health and improve quality of life for people living with knee osteoarthritis.
Source
Holiuk Y, Birsa R, Bukreieva T, et al. Effectiveness and safety of multiple injections of human placenta-derived MSCs for knee osteoarthritis: a nonrandomized phase I trial. BMC Musculoskeletal Disorders. 2025;26:418. doi: 10.1186/s12891-025-08664-2. PMID: 40281581; PMCID: PMC12032682. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC12032682/
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