What do people ask about a sore joint?

Sources

1. In a 480-patient, four-arm, multicenter randomized phase 2/3 trial, none of three orthobiologic cell injections - autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction, or allogeneic umbilical cord tissue-derived mesenchymal stromal cells - was superior to any other, or to a corticosteroid injection control, on pain at 12 months.

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

2. The International Society for Cell & Gene Therapy position statement holds that the acronym MSC should mean mesenchymal STROMAL cells and should only be called stem cells where rigorous in vitro and in vivo evidence of stemness exists for that specific preparation.

   Viswanathan S, et al. — Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT®) Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy, 2019. DOI: 10.1016/j.jcyt.2019.08.002.

3. The 2018 AAOS/NIH consensus work group recommended that minimally manipulated mixed cell preparations be called CELL THERAPY rather than stem cell therapy, and that their untested and uncharacterised nature be clearly communicated to patients and the public, because stem cells have properties these preparations do not meet.

   Chu CR, et al. — Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus Recommendations From the 2018 AAOS/NIH U-13 Conference. J Am Acad Orthop Surg, 2019. DOI: 10.5435/JAAOS-D-18-00305.

4. FDA states in its consumer alert that the only FDA-approved stem cell products in the United States are blood-forming stem cells derived from umbilical cord blood, approved for disorders of the blood-forming system, and that NONE of these products - stem cells, stromal vascular fraction, umbilical cord blood, Wharton's jelly or amniotic fluid - has been approved for the treatment of any orthopedic condition, including osteoarthritis, tendonitis, disc disease, tennis elbow, back pain, hip pain, knee pain, neck pain or shoulder pain.

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

5. 21 CFR 1271.10(a) sets the four criteria a human cell or tissue product must meet to be regulated SOLELY under section 361 of the Public Health Service Act: it must be minimally manipulated; intended for homologous use only, as reflected by labeling and advertising; not combined with another article beyond water, crystalloids or a preserving agent; and either have no systemic effect and not depend on the metabolic activity of living cells, or else be for autologous use, use in a close blood relative, or reproductive use.

   US Code of Federal Regulations, Title 21 — 21 CFR 1271.10 - Are my HCT/P's regulated solely under section 361 of the PHS Act. , 2004.

6. On 18 December 2024 FDA approved RYONCIL (remestemcel-L-rknd), the first mesenchymal stromal cell therapy ever approved in the United States - for steroid-refractory acute graft-versus-host disease in pediatric patients 2 months and older, given as eight intravenous infusions. It is not an orthopedic product and does not make any joint injection approved.

   US Food and Drug Administration — FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease. , 2024.

7. A 2025 systematic review and meta-analysis of 8 randomized trials in 502 patients found intra-articular mesenchymal stem cells improved WOMAC scores versus control at 6 months (MD 7.44, 95% CI 1.45-13.42) and 12 months (MD 10.31, 95% CI 0.96-19.67), with wide confidence intervals and a small pooled sample.

   Cao M, 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. DOI: 10.1186/s13287-025-04252-2.

8. A 2025 meta-analysis of 73 double-blind placebo-controlled injection trials in 5,895 knee osteoarthritis patients found placebo responder rates above 50 percent at 1, 3 and 6 months, declining by 12 months - which is why any uncontrolled 'our patients improved' claim from a clinic is uninterpretable.

   Previtali D, et al. — Placebo response to intra-articular injections in knee osteoarthritis: magnitude, evolution over time, and influencing factors. A systematic review and meta-analysis with meta-regression. EFORT Open Rev, 2025. DOI: 10.1530/EOR-2025-0022.

9. A 2024 systematic review of bone marrow aspirate concentrate for HIP osteoarthritis found the clinical evidence base thinner than for the knee, with most studies uncontrolled - the joint matters, and evidence does not transfer across joints.

   Chandrashekar S, et al. — Safety and Efficacy of Bone-Marrow Aspirate Concentrate in Hip Osteoarthritis: A Systematic Review of Current Clinical Evidence. Indian J Orthop, 2024. DOI: 10.1007/s43465-024-01183-7.

10. On 27 September 2024 the Ninth Circuit held in United States v. California Stem Cell Treatment Center that stromal vascular fraction produced by enzymatically digesting a patient's own fat IS a drug under the Federal Food, Drug, and Cosmetic Act, and that the same surgical procedure exception does not apply because the removed fat and the implanted SVF are not the same thing. The district court's ruling for the clinics was reversed.

    United States Court of Appeals for the Ninth Circuit — United States v. California Stem Cell Treatment Center, Inc., No. 22-56014 (9th Cir. Sept. 27, 2024). , 2024.