Executive Summary
Knee osteoarthritis is one of the most common and disabling joint conditions in the world. It affects nearly one in five people over the age of 45, and over a third of those aged 60 and older. The condition causes persistent pain, stiffness, and difficulty with daily activities such as walking, climbing stairs, and even sleeping comfortably. For many people, knee osteoarthritis is a daily reminder of reduced independence and declining quality of life. It is also an enormous financial burden. In Australia alone, the average patient costs the healthcare system more than AUD$20,000 per year, while global costs run into tens of billions annually. With populations ageing and obesity rates climbing, the number of people living with osteoarthritis is expected to rise sharply in the coming decades.
Despite its impact, treatment options for knee osteoarthritis remain limited. Current treatments such as exercise therapy, painkillers, and anti-inflammatory medications offer some relief, but the effects are usually modest and often the medications come with side effects if used long-term. Injections such as steroids may temporarily help with pain, but do not change the underlying disease. Ultimately, many people progress to needing knee replacement surgery, which, while effective, is invasive, expensive, and not without risks.
One of the biggest gaps in osteoarthritis care is that no widely available treatment has been proven to stop or slow down the structural damage to the joint itself. Most current therapies treat the symptoms rather than the root cause. This is why there has been growing interest in regenerative therapies such as stem cells, which may have the potential not just to reduce pain but also to protect and repair the joint.
Our Solution
Stem cells are unique cells with the ability to develop into different types of tissue, and they also release molecules that can help reduce inflammation and promote healing. For osteoarthritis, the hope is that injecting stem cells directly into the knee joint could slow down cartilage loss, improve joint function, and provide longer-lasting pain relief.
Over the past decade, stem cell injections have become widely marketed and increasingly popular among patients. Many clinics now offer stem cell treatments for knee osteoarthritis, often at a cost of thousands of dollars per injection. Some patients report feeling better after these treatments. However, the scientific evidence supporting their safety and effectiveness is still weak. Most studies so far have been small, of variable quality, or lacked proper comparison groups. This makes it difficult to know whether improvements are truly due to the stem cells or simply to placebo effects, natural fluctuations in pain, or other factors.
Because of this, there is an urgent need for high-quality, large-scale clinical trials to test whether stem cell injections really work. Patients, doctors, and policymakers need trustworthy data before stem cells can be recommended as a routine treatment for osteoarthritis.
The SCUlpTOR Trial
The SCUlpTOR trial (Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis) has been designed to fill this critical evidence gap. It is one of the largest and most rigorous studies of stem cell injections for knee osteoarthritis ever undertaken.
Some features that make the SCUlpTOR trial unique include:
1. Large sample size and robust design
The study has enrolled 320 participants, making it one of the biggest stem cell trials for knee osteoarthritis worldwide. It is a phase III randomised, double-blind, placebo-controlled trial—the “gold standard” of clinical research. This means participants will be randomly assigned to receive either stem cell injections or a placebo (saline solution), and neither the patients nor the doctors assessing them will know who received which treatment until the end of the trial.
2. Novel stem cell product
The trial is testing Cymerus™ mesenchymal stem cells, which are manufactured from induced pluripotent stem cells (iPSCs). Unlike stem cells harvested from a patient’s own fat or bone marrow, which require additional surgery and vary in quality, these cells come from a single healthy donor and are produced using a highly controlled process. This “off-the-shelf” approach means the therapy could be more accessible, standardised, and scalable if proven effective.
3. Dual focus on symptoms and structure
Previous trials have mostly focused only on pain or function. The SCUlpTOR trial is measuring both patient-reported pain outcomes and structural changes in the knee joint using advanced MRI imaging.
The two main outcomes are:
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- The proportion of participants achieving a “patient-acceptable symptom state” for knee pain after 24 months.
- Changes in cartilage thickness in the central part of the knee joint.
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By addressing both symptoms and structural changes, the trial will provide a much clearer picture of whether stem cells can truly modify the disease rather than simply masking it by relieving symptoms.
4. Cost-effectiveness analysis
Given the high price of stem cell injections, the trial will also assess whether the treatment offers good value for money compared to standard care. This is vital for health systems and insurers deciding whether such therapies should be reimbursed.
5. Patient involvement
People living with knee osteoarthritis have been directly involved in shaping the study design, ensuring the trial addresses outcomes that really matter to patients, such as pain relief, function, and quality of life.
The SCUlpTOR Trial Participation
Participants in the trial are adults over 40 with painful knee osteoarthritis of mild to moderate severity. Eligible participants are randomly assigned to receive three injections into the knee: at the start, at week three, and at one year. The injections are guided by ultrasound for accuracy. One group receives the Cymerus™ stem cells, while the other receives a saline placebo.
All participants are followed up for two years, with regular surveys about pain and function, as well as MRI scans at the beginning and end of the study to measure changes in cartilage. Blood and urine tests are also carried out to monitor safety.
As osteoarthritis treatments can affect pain perception, participants are asked to avoid new treatments during the study and to limit use of painkillers, except for occasional paracetamol for rescue pain relief.
The SCUlpTOR Trial Impact
The results of the SCUlpTOR trial could have a major influence on how knee osteoarthritis is treated worldwide.
- If the trial shows stem cell injections are effective:
They could become a new mainstream therapy, offering patients not just relief from pain but also protection against joint damage. Having a rigorously tested, standardised product could help regulate a market currently filled with unproven and costly treatments. Patients could have access to a therapy that delays or reduces the need for knee replacement surgery, potentially saving health systems billions in surgical costs.
- If the trial shows no significant benefit:
It would protect patients from spending large amounts of money on an ineffective treatment, allowing resources to be redirected towards more promising therapies or preventive strategies.
Regardless of the outcome, the findings will provide much-needed clarity in a field clouded by hype and uncertainty.
The SCUlpTOR Trial is Novel
The SCUlpTOR trial is the first large-scale randomised controlled trial to test an allogeneic, iPSC-derived stem cell therapy for knee osteoarthritis. It is also the first to combine rigorous symptom outcomes with detailed structural imaging and cost-effectiveness data. This multi-pronged approach ensures the results will be relevant not just for scientists and clinicians, but also for patients, policymakers, and healthcare funders.
The novelty lies in:
- Testing a next-generation stem cell therapy produced with high consistency and without the variability of patient-derived cells.
- Using state-of-the-art MRI measures of cartilage to detect subtle but meaningful changes in joint structure.
- Incorporating patient-centred outcomes and real-world measures of quality of life and cost, ensuring findings can directly guide care and policy.
The SCUlpTOR Trial Timeline
Recruitment for the SCUlpTOR trial began in 2021 across Sydney and Hobart, Australia. Participants are followed for two years after their first injection. Final follow-up visits and MRI scans are expected to be completed in late 2025. Once data cleaning, statistical analysis, and peer review are completed, the main results are expected to be released in early 2026.
These results will be shared widely through scientific conferences, journal publications, and public communication channels, ensuring that patients and the wider community are informed.
Extended follow-up of participants to see if there are enduring effects (such as sustained symptom relief, delay in knee replacement, etc) and impact of the treatment for a further three years is planned for 2026 to 2028.
The SCUlpTOR Trial and AOWA
The SCUlpTOR trial is being led by an independent team of academic researchers and is funded through a National Health and Medical Research Council (NHMRC) Grant (APP1162874). This government support ensures that the study is conducted with the highest standards of scientific and ethical integrity, free from commercial bias. Importantly, the investigational stem cell product, Cymerus™ MSCs, has been provided at no cost by Cynata Therapeutics Ltd (Carlton, Victoria, Australia). While Cynata supplied the study treatment and offered feedback on the trial design, they have no role in the analysis, interpretation, or reporting of results, which will remain entirely under the control of the academic investigators.
We gratefully acknowledge the invaluable support of Arthritis Osteoporosis Western Australia (AOWA), who are contributing $266,822 over three years to fund a part-time trial coordinator. The trial coordinator plays an important role in the smooth execution, follow-up, and close-out of this landmark Phase 3 study in knee osteoarthritis. They will ensure timely participant follow-up through to the final 24-month visit and beyond, enabling the collection of high-quality outcome data and maximising participant retention. This is critical for the scientific validity of the trial and for ensuring that the results are robust enough to influence clinical practice and policy.
As the SCUlpTOR trial is investigating a novel stem cell therapy that has the potential to both relieve symptoms and slow structural disease progression, the coordinator’s role in managing data integrity, coordinating multidisciplinary teams, and ensuring regulatory compliance is essential to delivering reliable results that could directly benefit people living with OA.
Importantly, the coordinator will also oversee extended follow-up to assess the durability of treatment effects out to five years ((such as whether benefits of stem cell therapy are sustained, whether knee replacement surgery can be delayed), providing rare and valuable long-term evidence on a promising disease-modifying approach. This aligns with AOWA’s mission to support innovative research with real-world impact on the prevention and management of arthritis.
Conclusion
Osteoarthritis is a leading cause of pain and disability, and millions worldwide are seeking better treatments. Stem cell therapy has generated much excitement, but until now, high-quality evidence has been limited. The SCUlpTOR trial is a landmark study that will provide reliable data on whether stem cell injections truly benefit people with knee osteoarthritis.
By testing both symptom relief and structural changes, and including cost-effectiveness analysis, the trial will produce evidence that is scientifically robust, clinically meaningful, and directly relevant to healthcare decision-making. Whether results are positive or negative, SCUlpTOR will guide doctors, patients, and policymakers toward informed decisions and could reshape the future of osteoarthritis care. Results are expected in early 2026, marking a pivotal moment for research and treatment.
Acknowledgement to AOWA
We sincerely thank AOWA for their visionary support of the SCUlpTOR trial. Funding the trial coordinator ensures smooth execution, high-quality follow-up, and reliable data collection, which are critical to the success of this world-leading study. We look forward to sharing the trial outcomes with the community and patients whose care could be transformed by this research.
Author:
Professor David Hunter
MBBS (Hons), MSc (Clin Epi), M SpMed, PhD, FRACP (Rheum)
Professor David Hunter is the Florance and Cope Chair of Rheumatology and Professor of Medicine at the University of Sydney. He serves as a Staff Specialist at Royal North Shore Hospital and leads the osteoarthritis research team at the Kolling Institute.
