Is One Knee Stem Cell Injection Enough? How to Choose Dose, Injection Frequency, and Treatment Course

There is currently no fixed “treatment course” suitable for all patients.

Relevant 2026 clinical recommendations state that one intra-articular MSC injection per year may be considered, but this recommendation has evidence level B and weak recommendation strength, meaning that uncertainty remains about the optimal injection frequency.

There is currently no clearly unified standard protocol. Different MSC products vary substantially, for example:

These factors all affect the actual dosing plan. At this stage, the plan is better determined according to the specific cell product, osteoarthritis severity, and previous treatment history.

Most existing clinical data observe patients for 6 to 24 months after treatment. Many patients show pain reduction and improved knee function 6 to 12 months after treatment.

Some data suggest treatment benefit can last more than 1 year, and longer follow-up has also observed some improvement. However, as time passes, the effect gradually weakens in some patients.

Relevant 2026 clinical recommendations state that one MSC injection per year can serve as a current reference plan. This suggestion is mainly based on the dosing methods and observation results in existing clinical data.

Most published MSC clinical data for knee osteoarthritis use a single intra-articular injection, with only a small number using two injections or periodic repeated injections.

At the same time, most treatments show clinical benefit over the following 6 to 12 months.

Therefore, balancing current evidence and treatment risk, once per year can serve as a relatively cautious clinical reference.

MSC doses used in existing knee osteoarthritis clinical trials vary greatly. The common range is approximately 1.0×10⁷ to 4.0×10⁸ cells per knee, meaning from about 10 million to 400 million cells.

This large difference is related to different MSC sources, culture methods, cell products, and clinical protocols.

The currently better supported moderate dose range is 2.5×10⁷ to 5.0×10⁷ cells per knee, or about 25 million to 50 million cells.

If cells can have therapeutic effects, does a larger injection number mean a better effect? It cannot be understood so simply.

Increasing the cell dose may enhance short-term local biological effects, but more cells inside the joint cavity may also increase local inflammation and tissue reaction.

Therefore, MSC therapy focuses on controlling risk while achieving enough clinical benefit, rather than pursuing the maximum cell number.

Some data have compared single and repeated injections.

A meta-analysis including 16 randomized controlled trials and 622 patients with knee osteoarthritis found that repeated injections may produce better clinical effects 6 to 12 months after treatment compared with a single injection. This suggests repeated dosing may prolong or enhance benefit in some patients.

However, another issue was also observed: patients receiving repeated injections had a higher proportion of mild adverse events. Each additional intra-articular injection adds one more local treatment exposure and increases the chance of pain, swelling, and other transient reactions.

Exercise rehabilitation is still needed after MSC treatment. The specific start time and training intensity should be determined according to pain, swelling, and joint function.

The following are usually introduced gradually:

Appropriate exercise helps improve peri-knee muscle strength and stability and is also an important part of long-term knee osteoarthritis management.

High-intensity weight-bearing exercise is not suitable immediately after injection. Increasing large mechanical loads too early may increase knee pressure and is not helpful for recovery of the local intra-articular environment.

Patients sometimes use follow-up MRI as the main standard for judging whether treatment has succeeded.

At present, symptom and functional improvement are more recommended as the main evaluation basis.

Common indicators include:

Pain VAS score: mainly observes changes in pain intensity.

WOMAC score: evaluates pain, joint stiffness, and daily activity ability.

KOOS score: in addition to symptoms and function, it can further evaluate sports ability and quality of life.

MRI can be used as an auxiliary examination to observe structural changes in cartilage, subchondral bone, synovium, and meniscus.

MSC treatment for knee osteoarthritis is still in the process of standardization.

First, cell sources differ greatly across studies. Second, doses range from 10 million to 400 million cells, a wide span. Third, clinical data on repeated injection remain much fewer than data on single injection. Fourth, most follow-up is concentrated at 6 to 24 months, so there are not enough data on long-term benefits and risks of repeated injections over many consecutive years.