Straight answers about sore joints and clinic care

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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. 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.

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. 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.

7. 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.