Stem Cell Injections for Knee Osteoarthritis: Are They Safe?

 By Dr Markandaiya Acharya, MBBS, MS Orthopaedic Surgeon, Cuttack Reg No. 22788 (OCMR)

A 58-year-old schoolteacher. Let us call her Sunita. She is not a real patient of mine, but you will recognise her.

Her right knee has been hurting for three years. First it was only the stairs. Then it was getting up from the floor after puja. Now she plans her whole day around how far she has to walk.

One evening her nephew sends her a video. A clinic is offering "stem cell injections" that claim to regrow knee cartilage. No surgery. No hospital stay. One sitting.

She watches it four times. Then she asks the question I hear in my clinic almost every week:

"Doctor, is it safe? And will it save me from a knee replacement?"

Those are two different questions. A recent systematic review answers the first one fairly well. The second one is still open. Both deserve an honest answer.

The problem: a knee that keeps shrinking your life

Knee osteoarthritis is the gradual wearing of the smooth cartilage that cushions the joint. As it thins, the knee becomes painful, stiff and swollen.

Patients rarely describe it in medical terms. They say:

• "My knee pain is worse when I climb stairs."
• "I cannot sit cross-legged or squat any more."
• "The knee is stiff in the morning and loosens after a few steps."
• "I hear a grinding sound when I bend it."

Tablets help for a while. Then they help less. The word "replacement" starts to come up, and most people are frightened of it. So anything that promises to avoid surgery sounds like the answer.

The mystery: what is actually inside a "stem cell injection"?

This is where the confusion begins. "Stem cell injection" is not one treatment. It is a label used for several quite different products:

• Bone marrow-derived cells, taken from your own pelvic bone, sometimes called BMAC (bone marrow aspirate concentrate).
• Fat-derived cells, taken from your own abdominal or thigh fat. These may be used straight away (SVF, or stromal vascular fraction) or grown in a laboratory for weeks before injection (cultured adipose-derived cells).
• Umbilical cord or placental cells, which come from a donor and not from your own body.

Two clinics can both advertise "stem cell therapy for knee pain" and be injecting completely different things, prepared in completely different ways.

So before asking "does it work?", a sensible patient asks something more basic. What are the side effects of stem cell injections in the knee?

The discovery: what 1,924 patients tell us about safety

A team of researchers set out to answer exactly that. Their systematic review, published in the HSS Journal, looked at studies of stem cell-based knee injections published between January 2000 and June 2021.

They screened 427 studies and included 48 of them, covering 1,924 patients. The studies included randomised controlled trials as well as prospective and retrospective studies.

Here is what they found.

1. Minor, short-lived reactions were fairly common.
Overall, 12.3% of patients had a transient adverse event. That is roughly one patient in eight. The most frequent were swelling and pain at the injection site, and these settled in less than four weeks.

2. No major complications were reported.
Across the included studies, there were no reported cases of infection, fat embolism or other medical complications. The authors concluded that, in the short term, injections of a patient's own (autologous) mesenchymal stem cells posed no risk of major complications such as infection, sepsis, tumour formation, embolism or death.

3. The type of cell mattered.
Reactions were not evenly spread. Umbilical cord-derived injections had a 51.7% rate of these transient events, and laboratory-cultured fat-derived cells had 29.5%. Both were significantly higher than bone marrow-derived and SVF injections.

In plain words: if Sunita had a donor umbilical cord product, a painful, swollen knee for some days afterwards would be about as likely as not.

Read the small print: what this study does not say

This is the part most advertisements leave out, so I will be direct about it.

It does not say stem cell injections work. The review measured complications. It did not set out to measure pain relief, function or cartilage regrowth. "Safe in the short term" and "effective" are separate claims.

It does not tell us about the long term. The authors themselves state that further long-term studies are needed before the safety profile can be called conclusive.

The studies were very different from each other. The authors point out significant variation in the protocol, the formulation, the timing and the location of injections. That makes a single neat conclusion harder to draw.

The reassurance on major complications applies to a patient's own cells. The conclusion about no major complications is framed around autologous injections, and donor-derived umbilical products showed the highest rate of reactions.

There is one more point from outside this paper. Whether these injections can regrow cartilage or delay a knee replacement is still under research, and leading international orthopaedic and arthritis guidelines do not currently recommend stem cell injections as routine treatment for knee osteoarthritis. That may change as better trials are published. For now, it remains an emerging treatment and not an established one.

The turning point: start with the knee, not the product

When someone like Sunita asks me about stem cells, I do not begin with the injection. I begin with her knee.

A proper assessment answers the questions that decide everything else:

• How advanced is the arthritis? A standing X-ray of the knee usually shows this clearly.
• Is the leg bowing? Alignment changes how the joint is loaded.
• Is the pain really from arthritis, or from the hip, the spine, a meniscus tear or an inflammatory condition?
• What has been tried properly so far, and for how long?

Many patients I see have never had a structured exercise programme. They have had tablets, a knee cap and advice to "avoid stairs". That is not a full trial of treatment.

The road to recovery: what has the strongest evidence?

The treatments with the most solid evidence for knee osteoarthritis are also the least glamorous:

• Strengthening exercises, especially for the thigh (quadriceps) and hip muscles, guided by a physiotherapist.
• Weight reduction where it applies. Every kilogram lost reduces the load on the knee.
• Activity changes, such as a Western-style toilet, a higher chair and a walking stick in the opposite hand.
• Pain relief medicines used sensibly and for short periods, after checking kidney, stomach and heart risk.
• Knee replacement surgery for advanced arthritis that no longer responds to the above. It remains a reliable operation for the right patient at the right time.

Where do injections fit? They are options that sit between these steps, and they should be discussed case by case.

If you are still considering a stem cell injection for knee osteoarthritis, ask the clinic these questions before you pay:

1. What exactly will be injected: my own bone marrow, my own fat, or a donor umbilical cord product?
2. Is it processed the same day, or cultured in a laboratory?
3. What results have been shown for my stage of arthritis, and in which published studies?
4. What reactions should I expect in the first four weeks, and whom do I call if the knee becomes hot, red or I develop a fever?
5. What is the total cost, and what happens if it does not help?
6. Is this being offered as part of an approved clinical trial?

A clinic that answers these plainly is worth listening to. One that promises regrown cartilage or a "permanent cure" is not.

The takeaway

The safety news is cautiously reassuring. In nearly two thousand patients, short-term problems after stem cell knee injections were mostly swelling and pain that settled within four weeks, and no major complications were reported.

Safety is only half of the decision, though. This research does not show that the injection will relieve your pain, rebuild your cartilage or keep you away from surgery. And we still lack long-term safety data.

So if you are in Sunita's position, do not decide from a video. Get your knee examined, get a standing X-ray, and find out which stage you are at. The right treatment depends on that, and for many people it is simpler and cheaper than they feared.

If knee pain is limiting your walking, your stairs or your sleep, consult an orthopaedic doctor near you. Patients in Cuttack, Banki, Bhubaneswar and nearby parts of Odisha are welcome to book a knee assessment with me and bring their X-rays and previous prescriptions along.

Frequently asked questions

Are stem cell injections safe for knee osteoarthritis?
In the short term, a systematic review of 48 studies and 1,924 patients reported no major complications. About 12.3% of patients had temporary swelling or pain at the injection site. Long-term safety is not yet established.

How long does swelling last after a stem cell injection in the knee?
In the studies reviewed, swelling and pain at the injection site lasted less than four weeks.

Which type of stem cell injection has more side effects?
In this review, umbilical cord-derived injections (51.7%) and cultured fat-derived cell injections (29.5%) had higher rates of temporary reactions than bone marrow-derived and SVF injections.

Can stem cell therapy help me avoid knee replacement?
This review did not study that question. Evidence on whether these injections delay or prevent knee replacement is still uncertain.

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Reference: Riggle C, McLellan M, Bohlen H, Wang D. Complications of Stem Cell-Based Injections for Knee Osteoarthritis: A Systematic Review. HSS Journal. 2024;21(4):476-484. doi:10.1177/15563316241271058

Disclaimer: This article is for patient education only and does not replace a consultation. Please see a qualified orthopaedic surgeon for advice about your own knee.