Patients with mild to moderate knee osteoarthritis, particularly Kellgren-Lawrence Grades 2 and 3, are often considered the strongest candidates for stem cell therapy. At these stages, cartilage damage is established, but meaningful joint structure usually remains.

Clinical studies have reported improvements in pain and function following mesenchymal stem or stromal cell treatment across several stages of knee osteoarthritis. Recent evidence also suggests that patients with less severe osteoarthritis may experience greater improvement than those with advanced Grade 4 disease.

This does not mean Grade 4 patients can never benefit. It means the treatment goal, expected response, and structural limitations become different as osteoarthritis progresses.

What Are the Different Grades of Knee Osteoarthritis?

One of the most commonly used systems for grading knee osteoarthritis is the Kellgren-Lawrence, or KL, scale. It uses X-rays to classify structural changes from Grade 0 to Grade 4.

• Grade 0: No visible signs of osteoarthritis.

• Grade 1: Very mild or uncertain changes. There may be possible joint-space narrowing or small osteophytes.

• Grade 2: Mild osteoarthritis. Definite osteophytes are present, and early joint-space narrowing may be visible.

• Grade 3: Moderate osteoarthritis. Joint-space narrowing becomes more obvious, with multiple osteophytes and possible changes in the underlying bone.

• Grade 4: Severe osteoarthritis. There is marked loss of joint space, larger osteophytes, significant changes in the underlying bone, and possible joint deformity.

The grade helps describe what an X-ray looks like, but it does not tell the entire story. Pain, mobility, alignment, muscle strength, activity level, and MRI findings may also influence treatment decisions.

Which Grade Usually Has the Best Opportunity to Respond?

For symptomatic patients considering regenerative treatment, Grades 2 and 3 often represent the most favorable treatment window.

At Grade 2, cartilage wear has begun, but substantial joint structure usually remains. Patients may notice pain during exercise, stairs, prolonged walking, or other activities.

At Grade 3, degeneration is more established. Joint-space narrowing is clearer, and symptoms may occur more frequently. However, enough cartilage and joint structure may still remain for a biological treatment to have a reasonable treatment target.

A systematic review specifically examining early to moderate knee osteoarthritis reported improvements in pain, function, and quality of life following MSC treatment in patients with KL Grades 1 to 3. More recently, the ESSKA-ORBIT European expert consensus found consistent clinical benefits from cell-based treatments in KL Grades 1 to 3, particularly for pain and function. Selected Grade 4 patients may also benefit, although outcomes are generally less favorable.

Can Grade 1 Knee Osteoarthritis Be Treated With Stem Cells?

Grade 1 represents very mild radiographic change, and not every patient at this stage needs an injection. Some people with Grade 1 changes have little or no pain. Exercise, weight management, muscle strengthening, activity modification, and other conservative strategies may be enough.

Stem cell therapy is therefore not recommended simply because an X-ray has been labelled Grade 1. If symptoms are persistent and there is additional evidence of cartilage injury on MRI, the treatment discussion may be different. This is one reason the patient’s symptoms and imaging need to be interpreted together. The goal should be to treat a clinically meaningful problem, not an X-ray grade alone.

Why Is Grade 2 Often a Good Stage for Regenerative Treatment?

Grade 2 osteoarthritis is considered mild but established OA. There are definite signs of degeneration, yet the joint has not usually reached major structural collapse. Much of the cartilage and normal joint architecture may still be present.

This creates an important treatment opportunity. UC-MSC therapy is studied primarily for its biological signaling and immunomodulatory effects. The aim is to influence inflammation and support the environment of the existing joint. The more useful joint structure that remains, the more realistic it is to consider biological treatment as part of a broader strategy involving strength, rehabilitation, weight management, and activity modification. This does not mean stem cells are required for every Grade 2 knee. Treatment should still depend on symptoms, previous treatment, function, and patient goals.

Can Grade 3 Knee Osteoarthritis Still Respond Well?

Yes. Grade 3 osteoarthritis is one of the most clinically relevant stages for considering regenerative treatment.

Patients at this stage often have clear symptoms and definite cartilage loss, but the knee has not necessarily progressed to end-stage collapse. Clinical studies of MSC therapy commonly include patients with Grade 2 and Grade 3 osteoarthritis and have reported improvements in pain and physical function. A 2026 analysis focused specifically on moderate KL Grade 2 to 3 disease described this group as an important treatment stage for regenerative strategies. The condition of the individual knee still matters.

A Grade 3 knee with reasonable alignment and remaining cartilage may be a more suitable biological target than a Grade 3 knee with major meniscal loss, instability, significant deformity, or extensive cartilage damage in several compartments. This is why two patients with the same OA grade may receive different recommendations.

Can Grade 4 Knee Osteoarthritis Respond to Stem Cell?

Some patients with Grade 4 osteoarthritis may still experience improvements in pain and function after MSC treatment. However, advanced structural damage limits what a biological treatment can realistically achieve.

Grade 4 knees may have marked cartilage loss, severe joint-space narrowing, bone changes, meniscal degeneration, and altered alignment. Stem cell therapy cannot mechanically restore these structures or reverse a substantially deformed joint.

The latest European expert consensus recognizes that selected Grade 4 patients may receive some clinical benefit from cell-based treatment, but outcomes are generally less favorable than in Grades 1 to 3. A 2026 systematic review also found that less severe osteoarthritis was associated with greater improvements in subjective pain following MSC-based injections. This does not make Grade 4 an automatic exclusion. It means expectations need to be different.

Why Does the Amount of Remaining Cartilage Matter?

Stem cell therapy does not replace an entire joint surface. MSCs are primarily studied for signaling effects that may influence inflammation, immune activity, and the biological environment of the joint.

When substantial cartilage and joint structure remain, there is more existing tissue to preserve and support. When cartilage loss has progressed to widespread bone-on-bone degeneration, the problem becomes increasingly structural and mechanical.

This helps explain why moderate osteoarthritis may provide a better opportunity for biological treatment than end-stage disease.It also explains why waiting until the joint is severely damaged before exploring every nonsurgical option may reduce the potential treatment window.

Does Stem Cell Regrow Cartilage in Grade 2 or Grade 3 Osteoarthritis?

Patients should separate symptom improvement from cartilage regeneration. Clinical studies have reported meaningful improvements in pain and function after MSC treatment. However, improvements on MRI have been less consistent.

A 2026 meta-analysis of randomized controlled trials found significant improvements in several pain and functional outcomes after MSC-based treatment, while MRI-based structural outcomes did not show consistent improvement.

A patient may therefore feel substantially better without showing dramatic cartilage regrowth on imaging. This does not mean the clinical improvement is unimportant. It means the treatment should not be presented as a guaranteed method for rebuilding lost cartilage.

Is the Osteoarthritis Grade Enough to Decide Treatment?

No. KL grade is useful, but it should not be used alone. Physicians also need to consider where the cartilage damage is located, whether one or several compartments are affected, joint alignment, meniscus condition, ligament stability, range of motion, swelling, muscle strength, body weight, and activity requirements.

Symptoms matter as well. One person with Grade 3 osteoarthritis may still walk several kilometres comfortably but experience pain after exercise. Another person with the same grade may struggle with stairs and ordinary daily activities. Their treatment goals are different. This is why medical evaluation should combine imaging with the patient’s actual level of pain and function.

Do You Need an MRI to Determine Whether Stem Cell Therapy Is Appropriate?

An X-ray is useful for determining the overall radiographic severity of osteoarthritis, particularly joint-space narrowing and alignment. MRI provides different information.

It can show cartilage damage, meniscal tears, bone marrow changes, ligaments, synovitis, and other structures that are not fully visible on an X-ray. MRI may therefore be especially helpful when symptoms do not match the X-ray, when the source of pain is unclear, or when the physician needs more detailed information before planning treatment.

The OA grade provides a starting point. The complete structure of the knee provides the treatment context.

Does Age Determine Whether Someone Will Respond?

Age can influence treatment response, but it is not the only factor. Joint condition is often more important than age alone. A physically active 65-year-old with Grade 2 osteoarthritis and good muscle strength may have a very different knee from a 55-year-old with severe Grade 4 degeneration, significant deformity, and major loss of function.

Clinical studies are increasingly examining patient characteristics that may predict response to MSC treatment. Disease severity, body composition, physical activity, cell characteristics, and biological markers may all influence outcomes. Treatment selection should therefore focus on the individual rather than using age as a simple cut-off.

When Is Knee Replacement More Appropriate?

Knee replacement becomes more relevant when osteoarthritis has progressed to severe structural damage with persistent pain and substantial loss of function.

A Grade 4 knee with significant deformity, severe joint-space loss, poor mobility, and symptoms that remain disabling despite nonsurgical treatment may be better served by surgical evaluation.

Stem cell therapy and knee replacement should not be viewed as competing versions of the same treatment. Stem cell therapy works with the existing joint. Knee replacement mechanically replaces severely damaged joint surfaces. The best option depends on how much usable joint structure remains and what is actually causing the patient’s symptoms.

What Grade Is the Best Candidate for Stem Cell Therapy?

There is no single grade that guarantees a successful response. However, current clinical evidence most consistently supports cell-based treatment in KL Grades 1 to 3, with symptomatic Grade 2 and Grade 3 osteoarthritis often representing the most practical treatment window.

Grade 1 patients may not need an injection if symptoms are minimal. Grade 4 patients may still experience symptom improvement, but severe cartilage loss and structural changes reduce what biological treatment can realistically accomplish. The decision should therefore be based on the combination of osteoarthritis grade, remaining cartilage, symptoms, alignment, function, imaging, and patient goals.

Frequently Asked Questions

• What grade of knee osteoarthritis responds best to stem cell therapy?

Clinical evidence most consistently supports MSC-based treatment in Kellgren-Lawrence Grades 1 to 3. Among symptomatic patients, Grades 2 and 3 often provide a favorable balance between established disease and remaining joint structure.

• Can stem cells help Grade 3 knee osteoarthritis?

Yes. Grade 3 patients are commonly included in clinical MSC studies, and improvements in pain and function have been reported. Treatment suitability still depends on cartilage condition, alignment, symptoms, meniscus health, and overall joint structure.

• Is Grade 4 too late for stem cell therapy?

Not necessarily. Selected Grade 4 patients may experience symptom improvement, but results are generally less predictable because the structural damage is more advanced. Stem cell therapy cannot recreate a severely collapsed joint surface.

• Should I get stem cell therapy for Grade 1 osteoarthritis?

Not automatically. Grade 1 changes can be very mild, and many patients may be managed with exercise, weight control, rehabilitation, and activity modification. Treatment should be based on symptoms and clinical findings rather than the grade alone.

• Can stem cells stop knee osteoarthritis from progressing?

Clinical studies have reported improvements in pain and function, but current evidence does not establish that MSC treatment reliably stops osteoarthritis progression in every patient. Maintaining strength, healthy body weight, appropriate activity, and addressing mechanical problems remain important parts of long-term management.

Medically reviewed by Dr. Naputt Virasathienpornkul, M.D. Orthopedic Surgeon, Sports Medicine & Joint Conditions

Related Reading

• Can Stem Cells Help a Bone-on-Bone Knee?
• Does Swelling After a Knee Stem Cell Injection Mean Something Is wrong? 
• Why Rehabilitation Matters After Stem Cell Therapy
• Can You Exercise After a Stem Cell Injection?

About EDNA Wellness

EDNA Wellness is a surgeon-led regenerative medicine center in Bangkok, specializing in orthopedic and neurological conditions using Umbilical Cord Derived Mesenchymal Stem Cells (UC-MSCs).

All cases are reviewed by orthopedic surgeons and neurosurgeons, with a focus on clinical indication, patient safety, and realistic treatment expectations. Stem cell therapy is recommended selectively, and alternative treatments are considered when more appropriate.

For more information or to book a consultation:

LINE: @ednawellness
WhatsApp: +66 (0) 64 505 5599
Website: www.ednawellness.com

References

• Cottmeyer DF, Chiu M, Maltusch K, Tsai LC. Towards optimized rehabilitation with regenerative therapy: A systematic review and meta-analysis on the effects of cell-based injections for knee osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy. 2026. https://pubmed.ncbi.nlm.nih.gov/41733018/
• The use of injectable orthobiologics for knee osteoarthritis: A formal ESSKA-ORBIT consensus. Part 2-Cell-based therapy. 2025. https://pubmed.ncbi.nlm.nih.gov/40923345/
• Stem cells for the treatment of early to moderate osteoarthritis of the knee: a systematic review. 2023. https://pubmed.ncbi.nlm.nih.gov/37804354/
• Efficacy and safety of intra-articular mesenchymal stem cell-based therapies in knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials. 2026. https://pubmed.ncbi.nlm.nih.gov/41863718/
• Tabet CG, et al. Advanced therapy with mesenchymal stromal cells for knee osteoarthritis: Systematic review and meta-analysis of randomized controlled trials. Journal of Orthopaedic Translation. 2024. https://pubmed.ncbi.nlm.nih.gov/39360004/
• Responders vs. non-responders to mesenchymal stromal cells in knee osteoarthritis: Mechanistic correlates of donor cell and patient features. 2026. https://pubmed.ncbi.nlm.nih.gov/42561945/