Knee osteoarthritis (KOA) is a chronic degenerative disease affecting the whole knee joint. As it progresses, patients may develop cartilage loss, synovial inflammation, subchondral bone change, osteophytes, and gradual structural degeneration.

Early and moderate disease is usually managed first with exercise rehabilitation, weight management, medication, and other non-operative treatments. In severe disease, some patients ultimately require total knee replacement. A major clinical challenge is how to relieve symptoms over the long term and slow the degenerative joint process. This is why mesenchymal stem/stromal cell therapy has entered the field of biologic treatment for KOA.

Mesenchymal stem/stromal cells (MSCs) are cells with self-renewal capacity, multilineage differentiation potential, and immunomodulatory properties. For KOA treatment, a properly prepared cell product is injected into the knee joint cavity.

Common sources include bone marrow, adipose tissue, umbilical cord, and cord blood. These sources differ in expansion capacity, immune characteristics, preparation methods, and clinical availability. Current evidence does not prove that one source is clearly superior for every patient.

Stem cell therapy is therefore not a single uniform product. Cell source, processing technique, cell quality, dose, and institutional quality control can all influence clinical results and safety.

MSCs may respond to inflammatory signals, migrate toward injured synovial and cartilage regions, and release biologically active factors. These paracrine effects may help regulate the joint immune environment, reduce inflammation, influence cartilage metabolism, and support synovial homeostasis.

Several randomized trials, systematic reviews, and meta-analyses suggest that intra-articular MSC injection can improve pain and knee function in some patients with KOA. A 2026 Chinese clinical expert consensus rated MSC injection for pain relief and functional improvement, with a potential positive role in slowing degeneration, as level A evidence with a strong recommendation.

One meta-analysis of 8 randomized trials including 502 patients found that MSC injection improved WOMAC, pain VAS, and KOOS outcomes at 6 and 12 months compared with control treatment. Another analysis used during consensus development included 8 MSC-versus-placebo datasets with 635 patients and showed a decrease in WOMAC scores after MSC treatment.

A pain-focused analysis including 9 studies and 475 patients also found better pain scores after MSC treatment than after placebo. Overall, the evidence supports a practical conclusion: in selected patients, intra-articular MSC injection may provide clinically meaningful symptom and function improvement.

Hyaluronic acid (HA) is a common intra-articular injection for KOA, mainly aiming to improve lubrication and symptoms. MSCs are cellular biologic therapies; beyond pain relief, their potential mechanisms include inflammation modulation, joint microenvironment effects, and cartilage metabolism.

Some direct comparisons suggest stronger improvement in pain and knee function with MSCs than with HA. A 2026 meta-analysis of 6 studies and 369 patients showed greater WOMAC improvement with MSCs, and another pain analysis of 8 studies and 483 patients showed greater VAS pain improvement with MSCs than with HA.

The clearest candidate group is adults with early-to-moderate KOA, especially Kellgren-Lawrence (KL) grade I to III disease, who have already received standard foundational treatment, rehabilitation, or medication but still have significant pain, activity limitation, and reduced quality of life.

Some patients with advanced KOA may have pain relief and functional improvement after MSC treatment, but results are generally less stable than in early-to-moderate disease. Advanced KOA may involve large cartilage defects, osteophytes, subchondral bone change, structural collapse, severe varus or valgus deformity, and major limb-alignment abnormality.

These are established mechanical and structural problems. Intra-articular cell therapy alone is unlikely to reverse severe bony deformity. KL grade IV end-stage disease therefore requires cautious assessment. If the joint is badly damaged, MSCs may temporarily reduce pain without changing the eventual need for knee replacement.

Most clinical follow-up currently ranges from 6 to 24 months. Many patients show clearer symptom and function improvement at 6 to 12 months. Some studies suggest longer persistence, while longer follow-up also shows that improvement may decline after 1 to 2 years.

Long-term knee management remains essential, including weight control, appropriate exercise, muscle strengthening, and avoidance of unreasonable joint overload.

Some long-term follow-up data suggest MSC intervention may reduce the later risk of total knee replacement in some patients, but the evidence is not yet strong enough to confirm that it reliably delays or prevents joint replacement.

Patients who already meet indications for knee replacement should not postpone necessary surgery indefinitely solely because they hope to preserve the joint.

Clinical MSC sources include bone marrow, adipose tissue, umbilical cord, and cord blood. Bone marrow-derived MSCs have more accumulated clinical data. Umbilical cord-derived MSCs have strong in vitro expansion potential, relatively low immunogenicity, and standardization potential. Adipose-derived MSCs are relatively accessible.

Studies differ substantially in culture conditions, passage number, cell viability, dose, and manufacturing process, so current evidence cannot conclude that one source is universally best.

Yes. Stem cell injection does not replace rehabilitation. Appropriate strengthening and exercise help improve periarticular muscle strength, stability, and whole-body function. After treatment, activity should be individualized according to pain, swelling, and joint function, then progressed gradually.

Early high-load exercise may increase mechanical stress across the knee, so recovery should not follow a fixed calendar alone. If the patient also has meniscus repair, osteotomy, or another operation, the rehabilitation protocol must follow the relevant surgical pathway.