For knee osteoarthritis treated with intra-articular mesenchymal stem/stromal cell (MSC) injection, the evidence is stronger for adults with early-to-middle stage knee osteoarthritis, especially those with imaging Kellgren-Lawrence (KL) grade I to III disease whose pain and activity limitation remain obvious after standard basic treatment, exercise rehabilitation, or routine medication.

Patients with late-stage disease may also have pain relief and functional improvement, but when the joint already has severe cartilage loss, bony structural change, or lower-limb alignment abnormality, intra-articular cell therapy alone is difficult to reverse these structural problems.

Knee osteoarthritis does not appear suddenly. As the condition gradually progresses, the knee may develop from relatively mild cartilage and intra-articular environmental changes to obvious cartilage wear, osteophyte formation, subchondral bone change, severe joint-space narrowing, and altered knee alignment.

Clinically, the Kellgren-Lawrence grade, or KL grade, is often used to classify knee osteoarthritis from grade I to IV according to X-ray findings.

A higher KL grade generally means more obvious structural degeneration of the joint.

The clearer candidate group at present is adults with early-to-middle stage knee osteoarthritis.

The relevant clinical recommendation in the 2026 Chinese expert consensus mainly considers the following patients:

Adults with KL grade I to III knee osteoarthritis who, after standard basic treatment, exercise rehabilitation, or routine medication, still have persistent joint pain or activity limitation that has clearly affected daily quality of life.

There are two conditions here: the disease is relatively early or middle stage, and the patient has already received a certain degree of standardized treatment, yet symptoms have not been satisfactorily controlled.

After MSCs enter the knee joint, their possible effects mainly include regulating inflammation, improving the local intra-articular microenvironment, and influencing cartilage metabolism and synovial status.

Although degeneration has already occurred in early-to-middle stage knee osteoarthritis, there is usually no severe complete cartilage loss, obvious joint-structure collapse, or severe bony deformity.

In this situation, the joint still retains relatively more tissue environment that can be biologically modulated. Therefore, placing MSCs preferentially among treatment options for early-to-middle stage knee osteoarthritis is supported by relatively more clinical data.

KL grade I usually represents relatively early imaging change. If symptoms are very mild and the patient can live normally through exercise rehabilitation, weight management, and other basic treatment, it is usually unnecessary to choose MSC treatment immediately only because the imaging grade is early.

If the patient is early stage but continues to have knee pain or activity limitation and remains unsatisfied after standard basic treatment, the doctor can further assess the specific situation.

KL grade II is one of the patient groups where current MSC-related clinical data are relatively concentrated.

At this stage, the knee has more definite degenerative change, but usually has not entered a severe structural-destruction stage.

If the patient has persistent pain, discomfort after activity, difficulty going up and down stairs, or clearly reduced sports ability, and standardized exercise rehabilitation and routine treatment have limited effect, intra-articular MSC injection can be one further treatment option.

The current recommended range includes KL grade III patients, and many clinical datasets have also included this stage.

In a long-term observation of KL grade III to IV patients, the average follow-up after treatment was about 4 years, and knee function and pain indicators improved compared with before treatment.

However, improvement in KL grade III patients was greater than in KL grade IV patients. This suggests that as joint structural damage becomes more severe, the room for MSCs to work may gradually decrease.

KL grade IV is a group that requires cautious consideration. Late-stage knee osteoarthritis may already have relatively severe structural changes, such as obvious cartilage loss, osteophyte formation, abnormal subchondral bone remodeling, joint-structure collapse, and lower-limb alignment shift.

MSCs may have some effect on the joint inflammatory environment and symptoms, but a single intra-articular injection alone cannot restore severely changed bony structures to normal.

In existing data, some KL grade IV patients can indeed obtain short-term or time-limited pain relief and functional improvement after treatment.

However, in patients with severe exposed subchondral bone and joint-structure collapse, cartilage repair remains limited even after relatively high-dose MSC treatment.

Therefore, even if symptoms temporarily improve in KL grade IV patients, total knee replacement may still be needed in the long term.

Age may be one factor influencing treatment response, but there is currently no simple age cutoff that determines that someone cannot receive treatment after a certain age.

Relatively younger early-to-middle stage patients may obtain a better treatment response, partly because of their own joint structure and disease severity.

If autologous MSCs are considered, age may also affect the cells themselves. As age increases, the proliferation and differentiation capacity of autologous MSCs may decline, which may affect cell preparation and treatment effect.

BMI, or body mass index, is closely related to the mechanical load borne by the knee joint. Patients with lower BMI may obtain a relatively better MSC treatment response.

When body weight is higher, the knee bears greater load during daily walking, stair climbing, and exercise.

Even if MSCs improve the inflammatory environment inside the joint, cartilage may continue to be damaged if the knee continues to bear large mechanical pressure.

Therefore, for overweight or obese patients, weight management usually remains an important part of long-term treatment for knee osteoarthritis.

The main treatment goals for knee osteoarthritis are to improve pain, function, and quality of life.

MRI can help observe cartilage, subchondral bone, synovium, meniscus, and other structures, but imaging changes and patient symptoms do not always correspond one-to-one.

Some patients have obvious degeneration on imaging but little actual pain; others have imaging changes that are not especially severe, yet daily activities are clearly affected.

Current recommendations more strongly support considering MSCs in patients who still have obvious symptoms after standard basic treatment. Basic treatment includes exercise rehabilitation, reasonable weight control, and routine medications.

If these treatments have been carried out in a standardized way for a period of time, but the patient still has persistent pain, restricted joint motion, or clearly affected daily life, further treatment options can be discussed with a sports medicine or joint specialist.