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2026.02.04
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Stem Cell Therapy for Knee Osteoarthritis: A Breakthrough in Regenerative Medicine for Chronic Knee Pain

How 100 million adipose-derived stem cells are helping patients worldwide avoid knee replacement

Your Knee Pain Has a Third Option — Beyond Pills and Surgery

Picture this. You’re in your 50s or 60s. You still want to play golf, hike mountain trails, or simply walk. But every step reminds you that the cartilage in your knee is disappearing.

Your doctor back home has given you two choices: keep taking anti-inflammatory drugs and cortisone shots that mask the pain while the joint deteriorates — or schedule a total knee replacement when you can’t take it anymore.

Sound familiar? You’re not alone. Knee osteoarthritis (OA) affects roughly 650 million people aged 40 and older worldwide, and those numbers are climbing every year. It is one of the leading causes of disability on the planet.

But here’s what your orthopedic surgeon may not have told you: there is now a scientifically validated third option.

Regenerative medicine — specifically, high-dose stem cell therapy — is rewriting the playbook for knee osteoarthritis treatment. And in 2025, one of the most rigorous meta-analyses ever conducted on the subject confirmed what forward-thinking physicians have long observed: injecting mesenchymal stem cells (MSCs) directly into the knee, without any surgery, can significantly reduce pain and restore joint function.

At Cell Grand Clinic in Osaka, Japan, we deliver exactly 100 million autologous adipose-derived stem cells into your knee joint — the precise high-dose protocol that the 2025 research identified as most effective. We do this under Japan’s Ministry of Health, Labour and Welfare (MHLW) oversight, one of the world’s strictest regulatory frameworks for regenerative medicine.

No surgery. No general anesthesia. No hospitalization. No long-term drug dependency.
What Does the Science Say? The 2025 Meta-Analysis Breakthrough

In March 2025, Cao et al. published a comprehensive systematic review in Stem Cell Research & Therapy, analyzing 8 randomized controlled trials (RCTs) involving 502 patients [2]. This rigorous study focused exclusively on intra-articular MSC injection without surgical intervention—providing the clearest evidence yet for stem cell efficacy in knee OA.

Stem cell therapy may avoid knee surgery. Stem cell thrapy is good option for Knee OA and pain.

Key Findings

Outcome Measure6-Month Results12-Month Results
WOMAC Total ScoreSignificant improvement (P=0.01)Significant improvement (P=0.03)
Pain (VAS)19.39-point reduction (P=0.0008)16.21-point reduction (P=0.0003)
KOOS SubscoresImproved across all domainsSustained improvement
Adverse EventsNo significant difference vs. controlSafe profile maintained

The meta-analysis concluded: “Intra-articular injection of MSCs alone could significantly improve knee pain and dysfunction in patients with unoperated OA” .

➤ Schedule Your Consultation with Dr. Wakabayashi

What’s Happening Inside Your Knee — and Why It Gets Worse

Think of knee cartilage as a precision-engineered shock absorber. In a healthy joint, this smooth tissue lets the bones in your knee glide against each other with almost zero friction. It distributes your body weight evenly and protects the underlying bone from impact.

In osteoarthritis, this cartilage breaks down. Microscopic cracks appear on the surface, deepen over time, and eventually, pieces break off entirely. When enough cartilage is lost, bone grinds directly against bone. That’s where the intense pain, swelling, stiffness, and grinding sensation (crepitus) come from.

The critical problem: adult cartilage cannot repair itself effectively. Unlike skin or bone, cartilage has no blood supply. Without blood flow, the body cannot deliver repair cells. Once cartilage damage begins, it tends to accelerate — creating a vicious cycle of inflammation, further loss, and escalating pain.

Where Are You on the Scale? The Kellgren-Lawrence Grading System

Doctors classify knee OA severity using the Kellgren-Lawrence (KL) system based on X-ray findings:

GradeX-Ray FindingsWhat You Feel
Grade 0Normal jointNo symptoms
Grade IPossible minor bone spurOccasional mild discomfort after heavy activity
Grade IIDefinite bone spurs, possible narrowingPain during and after activity, morning stiffness
Grade IIIModerate narrowing, multiple spursFrequent pain, difficulty with stairs and prolonged walking
Grade IVSevere narrowing or absent joint spaceConstant pain, severely limited mobility

Stem cell therapy achieves the best outcomes for patients with KL Grade II–III OA, where sufficient cartilage remains for the stem cells to support repair. Even some Grade IV patients experience meaningful pain relief.

Kellgren-Lawrence Grading System for Knee OA


How Stem Cell Therapy Works: The Science of Regeneration

Unlike hyaluronic acid (which merely lubricates) or corticosteroids (which suppress inflammation temporarily), mesenchymal stem cells initiate genuine biological repair through multiple mechanisms:

1. Anti-Inflammatory Action

Osteoarthritis involves chronic inflammation that actively destroys cartilage. MSCs secrete powerful anti-inflammatory molecules (IL-10, TGF-β, IL-1Ra) that work like internal fire extinguishers — they don’t just reduce today’s inflammation; they break the cycle causing ongoing damage.

2. Cartilage Protection and Repair

MSCs release growth factors that stimulate chondrocytes — the cells responsible for building and maintaining cartilage. Studies have documented measurable improvements in cartilage volume and quality following high-dose MSC injection.

3. Immune System Regulation

Through sophisticated paracrine signaling, MSCs regulate T cells, B cells, and macrophages within the joint [10]. This creates a microenvironment that favors tissue repair over destruction.

4. Sustained, Long-Term Pain Relief

By addressing inflammation, improving lubrication, and supporting tissue repair simultaneously, MSCs deliver pain relief that extends far beyond conventional injections. Clinical studies have documented sustained improvements at 12 months, 24 months, and up to 5 years post-treatment.

This is fundamentally different from a cortisone shot (wears off in weeks) or hyaluronic acid (lasts a few months at best). Stem cell therapy targets the root biological causes of your pain — not just the symptoms.

How Stem Cell Therapy Works: The Science of Regeneration for Knee OA and knee pain

Why Adipose-Derived Stem Cells Outperform Other Sources


Not all stem cells are created equal. The 2025 meta-analysis conducted subgroup analyses comparing different cell sources—and the results were striking:

Adipose-Derived MSCs (ADMSCs) vs. Bone Marrow MSCs (BM-MSCs)

OutcomeADMSCsBM-MSCs
6-Month WOMACSignificant improvement (P<0.00001)No significant improvement (P=0.27)
12-Month WOMACSignificant improvement (P<0.0001)No significant improvement (P=0.21)

Why adipose tissue wins:

  1. Higher cell yield: Abdominal fat provides significantly more stem cells than bone marrow, especially critical in elderly patients
  2. Easier harvesting: Liposuction is minimally invasive compared to bone marrow aspiration from the iliac crest
  3. Superior proliferation: Adipose-derived cells demonstrate robust expansion during culture
  4. Lower donor-site morbidity: No risk of prolonged pain at the harvest site

At Cell Grand Clinic, we exclusively use autologous adipose-derived stem cells harvested from your own abdominal subcutaneous fat—leveraging the most effective cell source identified in clinical research.

The Critical Importance of Cell Dosage: Why 100 Million Cells Matter

Perhaps the most clinically actionable finding from the 2025 meta-analysis was the dose-response relationship:

High-Dose (1×10⁸ cells) vs. Low-Dose (1-6.4×10⁷ cells)

Time PointHigh-Dose GroupLow-Dose Group
6-Month WOMACSignificant improvement (P=0.002)No significant difference (P=0.16)
12-Month WOMACSignificant improvement (P<0.0001)Marginal improvement (P=0.03)

The largest RCT included in the meta-analysis—Kim et al. (2023) with 252 patients—used 1×10⁸ (100 million) adipose-derived stem cells and demonstrated significant efficacy in patients with Kellgren-Lawrence grade 3 knee OA.

This is precisely why Cell Grand Clinic delivers 100 million cells per treatment—meeting the threshold that research has identified for optimal therapeutic benefit.

Comparison: Stem Cell Therapy vs. Surgery vs. Conventional Treatments

FeatureStem Cell TherapyHyaluronic AcidKnee Replacement
Primary GoalRegeneration & RepairTemporary LubricationArtificial Replacement
InvasivenessInjection onlyInjectionMajor surgery
Recovery TimeWalk same dayNone3-6 months rehabilitation
Duration of EffectYears Weeks to months15-20 years (prosthesis life)
Natural JointPreservedPreservedRemoved
Serious RisksMinimal (autologous cells)LowInfection, blood clots, implant failure

Why Cell Grand Clinic? What Sets Our Treatment Apart

Quality That Delivers Results

Many clinics advertise “same-day” stem cell treatments — they harvest cells and reinject them within hours. While convenient, the cell count is far too low to reach the therapeutic threshold identified by research. Some deliver fewer than 1 million actual stem cells. Ours deliver 100 million.

Stem cells are living organisms. Like any biological product, quality varies enormously. A “stem cell treatment” at one clinic can be fundamentally different from another based on how the cells are cultivated, stored, and delivered.

Our quality commitment: Fresh. Pure. Young.

Quality PillarOur StandardWhy It Matters
FRESH95%+ cell viabilityHigher viability = greater regenerative and repair potential. Dead or dying cells cannot heal. Cell Viability ≥98% (verified before every administration) vs. industry average of 70–85%
PURE~99% stem cell surface antigen expressionCD73+, CD90+, CD105+ expression ≈99%; CD45−, CD34− (contaminants eliminated) vs. many clinics that do not test
YOUNGPassage 3 cultivation; never over-expandedEarly-passage cells maintain maximum differentiation ability and biological activity. Over-passaged cells lose potency. Guaranteed 100 million cells at P3 vs. competitors using P5+ with reduced potency
GUARANTEED DOSE100 million cells per administration guaranteedTherapeutic dosing matters. Insufficient cell counts mean insufficient results.

All cells are processed at a GMP-compliant Cell Processing Center (CPC) certified under Japanese pharmaceutical standards — the same level of quality control applied to manufactured drugs.

Top stem cell quality for knee pain treatment

Japanese Government Approval: The World’s Gold Standard

Japan’s Act on the Safety of Regenerative Medicine (2014, regularly updated) created one of the world’s first comprehensive legal frameworks for stem cell treatments. Clinics must submit detailed treatment plans to MHLW-certified committees for review and approval.

13 certified treatment plans (Type II and III licenses)

Cell Grand Clinic holds One of the broadest portfolios of any regenerative medicine clinic in Japan. Our knee OA treatment is not “experimental” or “off-label.” It is a government-regulated medical treatment.

Compare this to the situation in many other countries, where stem cell clinics operate with little regulatory oversight, using uncharacterized cell preparations with no quality control requirements.

For more information about stem cells, click here.

Academic Partnership and Expert Oversight

Our cell culture protocols are developed in collaboration with Professor Takahiro Ochiya’s research team, whose work on exosomes and stem cell biology has appeared in top-tier journals. Every treatment plan is personally overseen by Dr. Yuichi Wakabayashi, Diplomate of the American Board of Regenerative Medicine, ensuring care that meets the highest international standards.

➤ Schedule Your Consultation with Dr. Wakabayashi

Treatment Process for International Patients

We’ve optimized our protocol for busy professionals and international visitors:

Step 1: Remote Consultation Share your MRI/X-ray results with our medical team for preliminary assessment.

Step 2: Visit 1 – Fat Harvest (Day 1) Minimally invasive fat harvest (~30 minutes) under local anesthesia. Return to your hotel immediately.

Step 3: Cell Culture (7 Weeks) Your cells are processed and expanded in our specialized CPC. Return home while we cultivate your cells to therapeutic levels.

Step 4: Visit 2 – Treatment (Week 8) Return to Osaka for stem cell administration via direct intra-articular injection (~30 minutes including preparation).

Note: Repeat treatments may be recommended depending on disease severity.

Treatment Process for stem cell therapy for Knee pain

Ideal Candidates for Stem Cell Therapy

This therapy is particularly effective for:

  • Kellgren-Lawrence Grade II-III OA: Patients with moderate degeneration typically see the best outcomes
  • Active individuals: Those who want to continue sports (golf, tennis, hiking) that may become impossible after joint replacement
  • Surgery-averse patients: Those who cannot or prefer not to undergo general anesthesia and prolonged rehabilitation
  • Patients seeking to delay surgery: Even in advanced cases, stem cell therapy can reduce pain and potentially postpone surgical intervention
Ideal Candidates for Stem Cell Therapy: Knee OA and knee pain.

Frequently Asked Questions

Q: How does this compare to total knee replacement?

A: Surgery replaces your joint with artificial components; stem cell therapy aims to preserve and repair your natural joint. For appropriate candidates, stem cell therapy can reduce pain by 50-80% and significantly improve mobility, potentially eliminating or delaying the need for surgery [12].

Q: Is there an age limit?

A: No strict limit. We have successfully treated patients in their 80s. The 7-week culture protocol is especially important for older patients, as it allows us to expand even cells with reduced proliferative capacity to therapeutic numbers.

Q: Can I walk immediately after treatment?

A: Yes. Unlike surgery, no cast or crutches are required. You can walk out of the clinic. We recommend avoiding high-impact activities for several weeks to allow cellular integration.

Q: How long do results last?

A: Clinical studies have shown sustained improvements at 12 months and beyond [2,11]. Individual results vary based on OA severity, activity level, and overall health.

Q: Is this treatment safe?

A: The 2025 meta-analysis found no significant difference in adverse events between stem cell and control groups [2]. Since we use your own cells (autologous), immune rejection is not a concern. The most common side effects are temporary pain and swelling at the injection site.

Conclusion: Restore Your Mobility—Naturally

Your knees are your foundation. Don’t replace them prematurely—restore them.

With the optimal combination of: –
Adipose-derived stem cells (the most effective source) –
100 million cells (the high-dose protocol) –
Japanese government regulatory approval (highest safety standards) –
7-week culture process (maximum potency)

Cell Grand Clinic offers the scientifically validated, non-surgical solution for knee osteoarthritis.

➤ Schedule Your Consultation with Dr. Wakabayashi

References

Cui AY, Li HZ, Wang DW, Zhong JL, Chen YF, Lu HD. Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. EClinicalMedicine. 2020;29-30:100587. Available from: https://doi.org/10.1016/j.eclinm.2020.100587

Cao M, Ou Z, Sheng R, Wang Q, Chen X, Zhang C, et al. Efficacy and safety of mesenchymal stem cells in knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Stem Cell Res Ther. 2025;16(1):122. Available from: https://doi.org/10.1186/s13287-025-04252-2

Wolfstadt JI, Cole BJ, Ogilvie-Harris DJ, Viswanathan S, Chahal J. Current concepts: the role of mesenchymal stem cells in the management of knee osteoarthritis. Sports Health. 2015;7(1):38-44. Available from: https://doi.org/10.1177/1941738114529727

Copp G, Robb KP, Viswanathan S. Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success. Cell Mol Immunol. 2023;20(6):626-650. Available from: https://doi.org/10.1038/s41423-023-01020-1

Kim KI, Lee MC, Lee JH, Moon YW, Lee WS, Lee HJ, et al. Clinical efficacy and safety of the intra-articular injection of autologous adipose-derived mesenchymal stem cells for knee osteoarthritis: a phase III, randomized, double-blind, placebo-controlled trial. Am J Sports Med. 2023;51(9):2243-2253. Available from: https://doi.org/10.1177/03635465231179223

Song N, Scholtemeijer M, Shah K. Mesenchymal stem cell immunomodulation: mechanisms and therapeutic potential. Trends Pharmacol Sci. 2020;41(9):653-664. Available from: https://doi.org/10.1016/j.tips.2020.06.009

Barry F. MSC therapy for osteoarthritis: an unfinished story. J Orthop Res. 2019;37(6):1229-1235. Available from: https://doi.org/10.1002/jor.24343

Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, et al. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci Transl Med. 2017;9(416):eaam7828. Available from: https://doi.org/10.1126/scitranslmed.aam7828

Maheshwer B, Polce EM, Paul K, Williams BT, Wolfson TS, Yanke A, et al. Regenerative potential of mesenchymal stem cells for the treatment of knee osteoarthritis and chondral defects: a systematic review and meta-analysis. Arthroscopy. 2021;37(1):362-378. Available from: https://doi.org/10.1016/j.arthro.2020.05.037

Thompson M, Mei SHJ, Wolfe D, Champagne J, Fergusson D, Stewart DJ, et al. Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: an updated systematic review and meta-analysis. EClinicalMedicine. 2020;19:100249. Available from: https://doi.org/10.1016/j.eclinm.2019.100249

Kim KI, Lee WS, Kim JH, Bae JK, Jin W. Safety and efficacy of the intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritic knee: a 5-year follow-up study. Stem Cells Transl Med. 2022;11(6):586-596. Available from: https://doi.org/10.1093/stcltm/szac024

Huang ZY, Zhang S, Cao MD, Lin ZJ, Kong L, Wu X, et al. What is the optimal dose of adipose-derived mesenchymal stem cells treatment for knee osteoarthritis? A conventional and network meta-analysis of randomized controlled trials. Stem Cell Res Ther. 2023;14(1):24. Available from: https://doi.org/10.1186/s13287-023-03239-1

This article is for informational purposes only and does not constitute medical advice. Consult with a qualified healthcare provider to determine if stem cell therapy is appropriate for your condition.

Last updated: February 2025

                           

【Author information】

若林雄一                                    

Yuichi Wakabayashi

                                   

CELL GRAND CLINIC
M.D., Ph.D.
Medical Director

                                   

【Specialty field】
Regenerative medicine, stem cell treatment, anti-aging medicine, preventive medicine, beauty aging care

【Affiliated academic societies/qualifications】
American Society for Regenerative Medicine specialist, Japan Anti-Aging Society specialist, radiology specialist, nuclear medicine specialist, member of the Japanese Society for Regenerative Medicine, member of the Japan Dementia Society, etc.                                        

【Biography】                                        
Graduated from Kobe University School of Medicine and completed Kobe University Graduate School (Doctor of Medicine). After gaining clinical and educational experience at Kindai University School of Medicine, he engaged in research at the National Institutes of Health (NIH). With a background in research in the field of neurological diseases, he specializes in regenerative medicine, anti-aging medicine, and preventive medicine. He has numerous achievements published in international journals, including reporting as the first author on "The world's first-in-human use of a PDE4B-specific PET drug" through joint research with Pfizer. We aim to provide medical care that extends the "healthy life expectancy" of each patient, emphasizing scientific evidence, safety, and quality control.