Most people with knee arthritis who end up asking about stem cells have already had a cortisone shot, or been offered one. The steroid injection is quick, inexpensive, covered by most insurance and often helps. So the obvious question is whether a stem cell injection does anything a cortisone shot does not: does it work better, last longer or protect the joint?
Until recently there was very little direct evidence to answer that. In 2023 a large randomized trial compared the two head to head, and its result is not the one either side of the debate would have chosen to advertise. This article sets out what that trial found, what is known about cortisone injections on their own, and how to think about the choice for your own knee.
The honest headline: in the largest head-to-head trial so far, none of three types of cell injection relieved knee pain better than a cortisone shot at one year, and none of the four groups showed a meaningful change on MRI. Cortisone has its own limits: its benefit usually fades within a few months, and repeated injections have been linked to faster cartilage loss. Neither option rebuilds a worn knee.
The quick answer
On current evidence, a stem cell injection has not been shown to relieve knee arthritis pain better than a cortisone shot over one year. In a 480-patient randomized trial published in Nature Medicine, injections of bone marrow concentrate, fat-derived cells and umbilical cord-derived cells were each compared with a corticosteroid injection, and none was superior on the main pain measures at 12 months.[1]
Where the two differ is in what is known beyond the first few months. Cortisone's pain benefit is best documented in the first weeks and appears to wear off by around six months.[2] Repeated cortisone injections every three months for two years caused more cartilage loss than saline in one well-run trial.[3] Cell injections avoid that particular concern, but they cost far more, involve a harvest procedure for most types, and their own benefit over placebo is uncertain.[6]
What each injection is
The cortisone shot
A corticosteroid, usually triamcinolone or methylprednisolone, is injected into the knee joint, often with a local anaesthetic. Steroids are powerful anti-inflammatory drugs. In an arthritic knee the lining of the joint is often inflamed, and calming that inflammation can reduce pain and swelling within days. The injection takes a few minutes in a clinic and needs no recovery time.
The stem cell injection
"Stem cell injection" covers several different products. Some clinics concentrate cells from your own bone marrow (BMAC), some process your own fat into a mix of cells called stromal vascular fraction (SVF), and some use mesenchymal stromal cells grown in a laboratory, from your own tissue or from donated umbilical cord tissue. The cells are thought to act mainly by releasing signals that dampen inflammation, rather than by turning into new cartilage. We cover the cartilage question in detail in our honest look at stem cells for knee osteoarthritis.
Side by side
| Cortisone shot | Stem cell injection | |
|---|---|---|
| How it is thought to work | Strong, direct anti-inflammatory drug effect inside the joint | Cells release signals that may reduce inflammation and modulate the joint environment |
| Procedure | A few minutes; no harvest; no downtime | Bone marrow or fat harvest for most types (not for donor cord cells), then an injection; same day or over several days |
| How fast it works | Often within days | Usually judged over weeks to months |
| How long benefit is documented | Clearest at 1–6 weeks; no evidence of an effect at 6 months in pooled trials | Reported over 6–12 months in trials, but not better than cortisone at 12 months in the largest comparison |
| Effect on cartilage | Repeated injections linked to more cartilage loss | No meaningful MRI change shown in the largest comparison |
| Guideline status | Strongly recommended for knee osteoarthritis by the 2019 ACR guideline | Not among the treatments the guideline recommends |
| Insurance | Usually covered | Usually not covered; paid out of pocket |
The head-to-head trial
The trial that matters most here was led by Emory University and published in Nature Medicine in 2023.[1] It enrolled 480 people with knee osteoarthritis graded Kellgren-Lawrence II to IV, from mild to severe on X-ray, across several US centres. Patients were randomized, three to one, to one of three cell injections or to a corticosteroid injection:
- Bone marrow aspirate concentrate from the patient's own pelvis
- Stromal vascular fraction from the patient's own fat
- Umbilical cord tissue-derived mesenchymal stromal cells from a donor
The main outcomes were two standard pain scores at 12 months. In the analysis of 440 patients, none of the three cell injections was superior to any other or to the corticosteroid control. None of the four groups showed a significant change in its MRI osteoarthritis score from baseline. No procedure-related serious adverse events were reported.
The trial has limits. It was single-blind rather than double-blind. It compared one injection of each product with one steroid shot and followed patients for a year, so it cannot tell us about repeated dosing or longer follow-up. But it is one of the largest randomized trials of cell injections for the knee, and it is the most direct answer available to the question in this article's title.
What the cortisone evidence shows on its own
Cortisone injections are not a neutral comparison: they have real benefits and real drawbacks.
Short-term relief is real but fades. A Cochrane review of 27 trials and 1,767 participants found that corticosteroid injections reduced pain more than control interventions, with a number needed to treat of about 8. The benefit was moderate one to two weeks after treatment, small to moderate at four to six weeks, small at 13 weeks, and there was no evidence of an effect at 26 weeks. The authors rated the evidence as low quality because the trials were small and inconsistent.[2]
Repeated injections may harm cartilage. In a two-year trial in JAMA, 140 people with knee arthritis and signs of joint inflammation received either 40 mg of triamcinolone or saline every 12 weeks. The steroid group lost significantly more cartilage on MRI (a mean of 0.21 mm versus 0.10 mm) and had no significant difference in knee pain compared with saline. The authors concluded the findings did not support that treatment pattern.[3]
Observational data point the same way. In the Osteoarthritis Initiative cohort, people who started knee corticosteroid injections had roughly three times the rate of worsening on X-ray as matched people who did not.[4] Because this was not a randomized study, people who receive injections may simply have had faster-progressing disease to begin with, so it shows an association, not proof of harm.
Rare but serious joint findings have been described. A 2019 review in Radiology described four adverse joint findings observed after hip and knee steroid injections: accelerated osteoarthritis, subchondral insufficiency fracture, complications of osteonecrosis, and rapid joint destruction with bone loss. The authors called for more research to understand how often these occur and who is at risk.[5]
None of this means a single cortisone shot is dangerous. For a flare of knee pain, it remains a reasonable, guideline-supported option, and the 2019 American College of Rheumatology and Arthritis Foundation guideline strongly recommends intra-articular glucocorticoid injections for knee osteoarthritis.[8] The concern is mainly with relying on repeated injections for years.
What the stem cell evidence shows on its own
Cell injections have their own uncertain evidence base. A 2024 meta-analysis of 16 randomized trials with 807 participants concluded that injecting mesenchymal stem cells for chronic knee pain from osteoarthritis probably provides little to no improvement in pain or physical function compared with control treatments, and may increase the risk of adverse events, including knee pain and swelling (low-certainty evidence).[6]
Some smaller trials have been more encouraging. In a 26-patient randomized phase I/II trial, two injections of umbilical cord-derived cells six months apart produced lower pain scores at 12 months than hyaluronic acid, while a single cell dose did not reach that difference; MRI scores did not differ. Several authors declared employment with a cell therapy company.[7] Results like this are a reason to keep studying repeated dosing, not proof that it works.
Key studies at a glance
| Study | Design | What it found |
|---|---|---|
| Mautner et al., Nat Med, 2023[1] | 480 patients randomized; three cell products vs corticosteroid; 12 months | No cell product superior to corticosteroid on pain; no significant MRI change in any group |
| Jüni et al., Cochrane, 2015[2] | 27 trials, 1,767 participants; corticosteroid vs control | Pain benefit greatest at 1–2 weeks; no evidence of an effect at 26 weeks; low-quality evidence |
| McAlindon et al., JAMA, 2017[3] | 140 patients; triamcinolone vs saline every 12 weeks for 2 years | More cartilage loss with steroid; no significant difference in pain |
| Sadeghirad et al., Osteoarthritis Cartilage, 2024[6] | 16 randomized trials, 807 participants; MSC vs control | Probably little to no improvement in pain or function |
| Bensa et al., KSSTA, 2025[9] | Safety data from 559 studies, 76,061 patients | At least one adverse event: 11.0% corticosteroid, 14.7% cell-based; severe events 1.1% vs 0.5%; infection 0.4% in both |
How the two compare on safety
A 2025 meta-analysis from the ESSKA Orthobiologics Initiative pooled adverse-event reports for different knee injections. Patients receiving cell-based therapies reported at least one adverse event slightly more often than those receiving corticosteroids (14.7% versus 11.0%), mostly non-severe, while severe adverse events were reported in 0.5% and 1.1% respectively, and infections in 0.4% of both groups.[9] The authors graded their evidence as Level IV, so these are rough comparisons across very different studies rather than a direct trial. Our article on whether stem cell injections are safe covers the side-effect research in more depth.
Who may be a reasonable candidate for a cell injection
Given the evidence above, we think a cell injection is most reasonable to discuss when someone:
- Has mild-to-moderate knee arthritis, with joint space still visible on a recent standing X-ray
- Has had cortisone shots that helped only briefly, or wants to avoid repeating them every few months
- Has already tried exercise therapy, weight management and standard pain relief
- Understands that the best trial so far found no advantage over cortisone at one year, and still wants to try it for their own reasons
- Is in reasonable general health, with no active infection or cancer
If you are also weighing platelet-rich plasma, our comparison of stem cells vs PRP for knee arthritis sets out that evidence.
When this may not be right for you
We would suggest staying with standard care, or seeing a knee surgeon, rather than travelling for a cell injection if:
- A single cortisone shot gives you months of relief and you need one only occasionally. The evidence does not show a cell injection would do better.
- Your X-ray shows bone-on-bone arthritis or significant deformity. No injection rebuilds a worn-out joint, and a knee replacement may be the better answer.
- The knee locks, catches or gives way, which can point to a mechanical problem that needs a surgical assessment.
- You have an active infection, active cancer, a bleeding disorder, or are pregnant or breastfeeding.
- The cost would be a financial strain, or you would only consider it worthwhile if it were certain to work. No honest clinic can promise that.
If you have had a steroid injection recently, or surgery may be on the horizon, tell us so the timing of any treatment can be planned with that in mind.
How to think about the decision
It may help to stop thinking of the two as rivals. A cortisone shot is a short-acting anti-inflammatory tool that works well for flares and should not be repeated indefinitely. A cell injection is an expensive, still-experimental option that, in the best comparison so far, did about as well as cortisone at one year. The realistic reason to choose cells is not that they are proven to work better, but that some patients want an alternative to repeated steroid injections and accept the uncertainty.
How our medical team assesses knees and other joints, and what treatment involves in Medellín, is set out on our page on stem cell therapy for knee, hip and joint conditions.
The bottom line
A stem cell injection is not a stronger cortisone shot. In the largest randomized comparison, cell injections relieved knee arthritis pain no better than corticosteroid at 12 months, and neither changed the joint on MRI. Cortisone works quickly but briefly, and repeated injections carry a cartilage concern. Cell therapy avoids that concern but costs more, has an uncertain benefit over placebo, and is not part of mainstream guidelines.
If you are trying to decide, send us a recent X-ray or MRI and tell us how you responded to previous injections. We will tell you honestly whether we think a cell injection is reasonable for your knee, and when we think standard care or a surgeon would serve you better.
