What to ask before a joint procedure

What to ask about marrow drawn and spun, called bone marrow aspirate concentrate

This long name means marrow is drawn from your pelvis. A machine spins it very fast. The spinning keeps a smaller amount for the joint procedure. That amount holds blood cells, platelets, fluid, and proteins. It isn't one pure kind of cell.

Ask what the clinic measured in your own sample.

A total cell number won't answer every question. It doesn't say how many early cells can change as they grow. The draw and spinning can change the mix. Ask why the number matters for your soreness.

What to ask when the procedure uses fat

Some procedures start with a small amount of your fat. A clinic may wash and cut it into tiny pieces. Another method pulls a mix of cells away from the fat. Those methods don't leave the same material.

Ask what will actually go into your joint.

Some clinics use enzymes, which are substances that break tissue apart. Others use cutting, washing, or spinning. Ask which method the clinic uses. Then ask whether research tested that same method. If the answer stays vague, you don't know what's offered.

What to bring to the procedure talk

Bring one short question: which material will you use? Ask where the blood, marrow, or fat comes from. Ask how it's washed, cut, or spun. Find out whether anything else gets added.

You don't need a lesson in cell science.

Find out how the clinic responds when soreness stays. A machine can prepare blood or tissue correctly. That alone doesn't prove the procedure will help. Ask whether people with your joint felt better afterward.

Sources

1. In 96 patients, concentrated bone marrow aspirate contained a mean of 26.3 million nucleated cells per mL but only about 1,422 colony-forming units of connective tissue progenitors, and the nucleated cell count had negligible predictive value for how many progenitor cells were actually present (r-squared 0.28).

   Muench LN, et al. — Nucleated Cell Count Has Negligible Predictive Value for the Number of Colony-Forming Units for Connective Tissue Progenitor Cells (Stem Cells) in Bone Marrow Aspirate Harvested From the Proximal Humerus During Arthroscopic Rotator Cuff Repair. Arthroscopy, 2021. DOI: 10.1016/j.arthro.2021.01.064.

2. Mesenchymal stromal cells make up only about 0.001 to 0.01 percent of the nucleated cells in bone marrow, so the harvesting and processing technique - aspiration site, syringe size, centrifuge speed and time - materially determines what ends up in the syringe, and no consensus protocol exists.

   Jeyaraman M, et al. — Impact of the Process Variables on the Yield of Mesenchymal Stromal Cells from Bone Marrow Aspirate Concentrate. Bioengineering (Basel), 2022. DOI: 10.3390/bioengineering9020057.

3. 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.

4. The 2005 International Society for Cellular Therapy statement that first flagged the problem concluded that plastic-adherent marrow cells do not meet generally accepted criteria for stem cell activity, making the name 'mesenchymal stem cell' scientifically inaccurate and potentially misleading to the lay public.

   Horwitz EM, et al. — Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy, 2005. DOI: 10.1080/14653240500319234.

5. A laboratory study of three commercially available amniotic fluid products marketed for orthopedic use found no viable mesenchymal stem cells in any of them when compared against unprocessed amniotic fluid and bone marrow-derived MSC samples - products sold as 'amniotic stem cell therapy' contained no living stem cells.

   Panero AJ, et al. — Are Amniotic Fluid Products Stem Cell Therapies? A Study of Amniotic Fluid Preparations for Mesenchymal Stem Cells With Bone Marrow Comparison. Am J Sports Med, 2019. DOI: 10.1177/0363546519829034.

6. 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.

7. A meta-analysis of 10 studies and 472 patients comparing bone marrow aspirate concentrate with adipose stromal vascular fraction for knee osteoarthritis found both improved pain scores and could not establish that either is superior to the other.

   Bolia IK, et al. — Clinical Efficacy of Bone Marrow Aspirate Concentrate Versus Stromal Vascular Fraction Injection in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis. Am J Sports Med, 2022. DOI: 10.1177/03635465211014500.

8. A randomized trial comparing commercially available systems in 71 patients found microfragmented adipose tissue equivalent to leukocyte-rich PRP on KOOS pain at 12 months.

   Baria M, et al. — Microfragmented Adipose Tissue Is Equivalent to Platelet-Rich Plasma for Knee Osteoarthritis at 12 Months Posttreatment: A Randomized Controlled Trial. Orthop J Sports Med, 2024. DOI: 10.1177/23259671241233916.

9. 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.

10. A CDC Notes from the Field report in MMWR documented infections in US patients during 2018 after receipt of bacterially contaminated umbilical cord blood-derived products used for indications other than blood or immune reconstitution.

    Perkins KM, et al. — Notes from the Field: Infections After Receipt of Bacterially Contaminated Umbilical Cord Blood-Derived Stem Cell Products for Other Than Hematopoietic or Immunologic Reconstitution - United States, 2018. MMWR Morb Mortal Wkly Rep, 2018. DOI: 10.15585/mmwr.mm6750a5.

11. 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.

12. FDA's final guidance for industry, issued July 2020 by CBER and CDRH under docket FDA-2017-D-6146, sets out how the agency applies the minimal manipulation and homologous use criteria that determine whether a cell or tissue product is a 361 HCT/P or an unapproved 351 biological product requiring a license.

    US Food and Drug Administration, CBER and CDRH — Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use - Guidance for Industry and Food and Drug Administration Staff. , 2020.

13. 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.