A knee that keeps limiting you is worth an exam

Returning soreness deserves a doctor's attention

Call for an appointment if aching lasts for several days, returns often, or limits your ordinary work. Trouble with stairs, sleep, balance, or rising from a chair matters during the exam too.

Tell the doctor when the ache started and which tasks make it better or worse. Don't leave out swelling, clicking, locking, or the feeling that your knee may give way.

Fever, redness, or sudden weakness needs care now

Call your doctor that day if heat and redness come with heavy swelling and fever; if you feel very sick or can't stand safely, go to the emergency room now. Quick care matters.

A warm, red, swollen calf after travel, surgery, or a long sit may warn of a clot in the blood. Seek help that day instead of waiting for your usual appointment.

The doctor checks bending, muscles, and the sore spot

The doctor will ask where it hurts, when it swells, and which daily jobs are harder. During the exam, you'll bend the knee while the doctor checks its muscles, balance, and sore areas.

Take the names of your medicines and any old X-ray or visit notes. A careful doctor won't skip your health history, earlier injuries, cost concerns, or the result you want.

Sources

1. The RESTORE trial - a participant-, injector- and assessor-blinded RCT of 288 adults aged 50+ with symptomatic medial knee OA (Kellgren-Lawrence 2-3) - compared three weekly intra-articular PRP injections against saline placebo, with co-primary endpoints of 12-month knee pain and medial tibial cartilage volume on MRI. PRP did not beat placebo on either. It is the single best-designed test of the specific claim that PRP changes joint structure, and it was negative.

   Bennell KL, et al. — Effect of Intra-articular Platelet-Rich Plasma vs Placebo Injection on Pain and Medial Tibial Cartilage Volume in Patients With Knee Osteoarthritis: The RESTORE Randomized Clinical Trial.. JAMA, 2021. DOI: 10.1001/jama.2021.19415.

2. A four-arm, multicentre, single-blind phase 2/3 randomized trial of 480 knee OA patients (KL II-IV) compared autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic umbilical-cord-tissue mesenchymal stromal cells against a corticosteroid injection control. At 12 months NONE of the three orthobiologic injections was superior to another, or to the corticosteroid control, and none of the four groups showed a significant change in MRI osteoarthritis score from baseline. No procedure-related serious adverse events occurred.

   Mautner K, et al. — Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.. Nature medicine, 2023. DOI: 10.1038/s41591-023-02632-w.

3. A GRADE-rated systematic review and meta-analysis of 16 randomized trials (807 participants) found that MSC therapy for chronic knee OA pain PROBABLY RESULTS IN LITTLE TO NO DIFFERENCE in pain relief at 3-6 months (WMD -0.74 cm on a 10 cm VAS against a minimally important difference of 1.5 cm) or physical functioning (WMD 2.23 on the SF-36 100-point subscale against a 10-point MID), both moderate certainty; at 12 months pain was again probably little-to-no-different (WMD -0.73 cm). The measured effect is real but sits BELOW the threshold at which a patient would notice it.

   Sadeghirad B, et al. — Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials.. Osteoarthritis and cartilage, 2024. DOI: 10.1016/j.joca.2024.04.021.

4. A 2026 systematic review and meta-analysis of 28 randomized trials of intra-articular mesenchymal stem cell-based therapies in knee OA found significant improvements in several pain and function measures (delta-VAS MD -1.67; KOOS pain MD 15.37) but NO significant difference in WOMAC, KOOS quality of life or the Lequesne index, and MRI-based WORMS scores were non-significant - indicating no consistent structural benefit. Its own conclusion: these therapies serve a primarily SYMPTOM-modifying rather than STRUCTURE-modifying role, with higher frequencies of local reactions to weigh against the symptomatic benefit.

   Awad G, et al. — Efficacy and safety of intra-articular mesenchymal stem cell-based therapies in knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.. Clinical rheumatology, 2026. DOI: 10.1007/s10067-026-08042-w.

5. The strongest recent POSITIVE signal: a meta-analysis of 10 RCTs (818 patients, KL I-III) found intra-articular MSC injection beat hyaluronic acid at 12 months on WOMAC total (MD -10.22), VAS (MD -1.31) and on the MRI Whole-Organ Magnetic Resonance Imaging Score (MD -26.01), all reaching the minimal clinically important difference, with no significant difference in adverse events. Recorded here at full weight: this result and the negative RESTORE and Mautner trials are both in the literature, and an honest page reports both.

   Jin WS, et al. — Mesenchymal Stem Cells Injection Is More Effective Than Hyaluronic Acid Injection in the Treatment of Knee Osteoarthritis With Similar Safety: A Systematic Review and Meta-analysis.. Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 2025. DOI: 10.1016/j.arthro.2024.07.027.

6. A JBJS systematic review screened 420 papers on intra-articular cellular therapy for knee OA and focal cartilage defects and found only SIX at Level III evidence or higher (4 Level II, 2 Level III), covering 300 knees, with wide variation in cell source, cell characterisation, adjuvant therapy and outcome assessment - meaning no consensus exists on indications, cell sources, preparation or delivery. Two products called 'stem cell therapy' at two clinics may share almost nothing.

   Chahla J, et al. — Intra-Articular Cellular Therapy for Osteoarthritis and Focal Cartilage Defects of the Knee: A Systematic Review of the Literature and Study Quality Analysis.. The Journal of bone and joint surgery. American volume, 2016. DOI: 10.2106/JBJS.15.01495.

7. A Level-1a systematic review of 87 randomized PRP-for-knee-OA trials (7,925 patients, 8,118 knees) scored them against the 23-item MIBO reporting checklist. The overall MIBO score was 72%, 71% of studies scored below 80%, and reporting was worst on exactly the items that define the product: whole-blood characteristics (20%), platelet recovery rate (22%), PRP analysis (30%), PRP activation (47%). Adherence did not improve after MIBO was published. Much of the PRP literature does not say what was actually injected.

   Nakagawa HF, et al. — Systematic Review of Randomized Controlled Trials Evaluating the Use of Platelet-Rich Plasma for Knee Osteoarthritis: Adherence to Minimum Information for Studies Evaluating Biologics in Orthopaedics.. The American journal of sports medicine, 2025. DOI: 10.1177/03635465241249996.

8. FDA states plainly that no stem cell, exosome, stromal vascular fraction, umbilical cord blood, Wharton's jelly or amniotic-fluid product has been approved for the treatment of ANY orthopedic condition - it names osteoarthritis, tendonitis, disc disease, tennis elbow, back pain, hip pain, knee pain, neck pain and shoulder pain individually. The only FDA-approved stem cell products in the United States are cord-blood-derived blood-forming stem cells for disorders of the hematopoietic system, and there are currently no FDA-approved exosome products.

   US Food and Drug Administration, Center for Biologics Evaluation and Research — Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. FDA, 2020.

9. An individual-participant-data meta-analysis of 621 placebo participants across 10 intra-articular injection trials found placebo response (>=20% pain reduction) was itself predictable: use of local anaesthetic and ultrasound guidance were associated with REDUCED odds of short-term placebo response, and longer trial duration with increased odds at midterm. Any single-arm 'our patients got better' claim about an injection is therefore uninterpretable.

   Zou K, et al. — Predictors of Placebo Response to Local (Intra-Articular) Therapy In Osteoarthritis: An Individual Participant Data Meta-Analysis.. Arthritis Care & Research, 2024. DOI: 10.1002/acr.25212.

10. A 2026 network meta-analysis of 21 RCTs (2,254 patients) found both leukocyte-poor and leukocyte-rich PRP significantly improved 6-12 month WOMAC function versus placebo (MD -10.54 and -13.20 respectively) and both were superior to hyaluronic acid, with leukocyte-poor PRP ranked first (P-score 0.96) — a materially more favourable read of PRP than the RESTORE trial, which is why this corpus presents both.

    Journal of Orthopaedic Surgery and Research authors — Leukocyte-rich versus leukocyte-poor platelet-rich plasma and hyaluronic acid for knee osteoarthritis: a systematic review and network meta-analysis.. Journal of Orthopaedic Surgery and Research, 2026. DOI: 10.1186/s13018-026-06689-4.