In its 2019 notification on exosome products, the FDA advised patients to ask whether the agency has reviewed the product, to ask the clinical investigator for the FDA-issued investigational new drug (IND) number and the FDA letter acknowledging it, and to read a consent form that names the institutional review board before signing [3]. The same three questions apply to a cell product, and together with nine more on the product, the tissue bank, state law, the certificate of analysis, who performs the procedure, adverse event reporting and the cost in writing, they make up the 12-item checklist in this guide.
A patient weighing an offer from a clinic can work through the 12 questions here, with why each one matters, what a documented answer looks like, and the public tools that let you check an answer yourself. Each question points to a document a clinic can show you, and the last section gathers them into a checklist you can print or save to your phone. ExaVeyra Sciences supplies mesenchymal stem cells to licensed practices, and whether any product suits a particular patient is a decision for that patient and their licensed practitioner.
Regulatory status
The FDA states that stem cell products generally require FDA approval, that the approved stem cell products consist of blood-forming stem cells derived from umbilical cord blood, and that none of the products it lists have been approved for any orthopedic, neurological, cardiovascular or pulmonary condition, autism, macular degeneration, blindness, chronic pain or fatigue [1]. One mesenchymal stromal cell product was approved in December 2024, for a pediatric transplant complication [25]. Other MSC products are section 351 biologics that reach a patient through a biologics license or an IND [6]. ExaVeyra supplies mesenchymal stem cells from an FDA-registered tissue bank to practices in states whose laws permit it, with the 351 biologic status applying everywhere, and the practitioner and their counsel decide whether and how any product is used.
The FDA’s own advice supplies the first three questions
In its 2019 safety notification on exosome products the FDA told patients considering those products to ask if the agency has reviewed it, to ask the clinical investigator for the FDA-issued IND number and the chance to review the FDA communication acknowledging the IND, and to confirm that information with their own health care provider before going ahead [3]. The same page says a consent form for an IND study identifies the institutional review board, and that a patient can ask the sponsor for the investigator’s brochure [3].
The 2021 patient page goes further. It states that a person who is being charged for these products or offered them outside a clinical trial is likely being deceived and offered a product illegally, and that inclusion in clinicaltrials.gov or registration with FDA does not mean a product is legally marketed [2]. The page invites anyone offered such a product to contact the agency at ocod@fda.hhs.gov [2].
An IND matters because federal law requires that a drug be the subject of an approved marketing application before it is transported across state lines, and the IND is the exemption a sponsor obtains for a clinical study [4]. A clinic that answers the IND question with a number, a sponsor name and an acknowledgment letter has placed its product inside that framework; a clinic that answers with a registration number has not [2, 4].
Marketplace studies explain why documented answers matter
Turner and Knoepfler first mapped the US direct-to-consumer market in 2016 and found widespread promotion of unapproved interventions by businesses based in the United States [8]. Their 2018 temporal analysis showed new business websites at least doubling on average each year from 2009 to 2014 and appearing at about 90 to 100 a year from 2014 to 2016, while FDA warning letters over the same period were limited [9]. By March 2021, Turner counted 1,480 businesses operating 2,754 clinics [7].
What those clinics tell patients has been measured. Murdoch and colleagues analyzed 243 complementary and alternative medicine clinic websites in 2018 and found statements of general risks on 24.69 percent, risks specific to the mode of therapy on 5.76 percent, regulatory status on 30.86 percent, and the experimental or unproven nature of what was offered on 33.33 percent [12]. Piuzzi and colleagues had a simulated 57-year-old patient with knee osteoarthritis call 273 US centers and found a mean quoted price of $5,156 for a same-day knee injection, with centers claiming good results in a mean of 82 percent of patients, against published evidence the authors describe as low level [11].
Fu and colleagues described in 2019 the credentials and scope of training of the physician and nonphysician practitioners working for US companies marketing these procedures, which is why the checklist asks who will perform yours and in what specialty they trained [10]. Snyder and colleagues documented patients crowdfunding the cost of unproven interventions, and Sipp and colleagues described the marketing as a global problem resistant to regulatory efforts [13, 14]. A clinic that volunteers documents answers all of this before you ask.
Twelve questions and the documented answer each one deserves
The table sets out the 12 questions in the order you would ask them, why each matters, and what a documented answer looks like. A spoken reassurance is an answer to none of them; each row names a document, a number or a public database entry.
| Question | Why it matters | What a documented answer looks like |
|---|---|---|
| 1. What exactly is the product, from which tissue, and is it my own cells or a donor’s? | The FDA lists adipose, cord blood, Wharton’s jelly and amniotic products separately, and none is approved for the uses clinics advertise [1] | A product name, the tissue source, autologous or allogeneic, and the manufacturer named in writing |
| 2. Which tissue bank or manufacturer made it, and what is its FDA registration number? | Registration is a listing duty under 21 CFR 1271.10, and the CDC report states it is not approval [6, 18] | An establishment name you can find in the FDA HCTERS public query, with its registered functions and products [5] |
| 3. Has the FDA reviewed this product, and is there an IND? | The FDA’s first question to patients; an IND is the lawful route for an investigational product [3, 4] | The IND number, the sponsor, and the FDA acknowledgment letter, which the FDA says you may ask to see [3] |
| 4. Is this product FDA approved? | The only approved MSC product is for pediatric transplant patients; cord blood products are approved for blood disorders [1, 25] | A product that appears on the FDA list of approved cellular and gene therapy products, or a plain statement that it does not [25] |
| 5. What does my state’s law say about this product? | Five states permit physicians to offer stem cell products under conditions, and two make selling them for investigational use a crime | The statute cited by section, the written notice the statute requires, and the supplier accreditation it names |
| 6. May I see the certificate of analysis for the lot I would receive? | Release testing is what separated the contaminated 2018 products from a documented lot [18, 23] | A lot-specific certificate showing sterility, endotoxin, mycoplasma, viability with the method, identity markers and donor serology [23, 24, 26] |
| 7. How was it shipped and stored, and can I see the temperature record? | A frozen cell product that warmed in transit is no longer the product on the certificate | Cold-chain records for the shipment and a freezer log at the clinic, available on request |
| 8. Who will perform the procedure, and what is their license and specialty? | Credentials and scope of training vary widely across clinics in this market [10] | A named licensed practitioner, their license number, and the specialty in which they trained |
| 9. What does the consent form say, and which review board approved it? | The FDA says an IND study consent form identifies the institutional review board [3] | A consent form that names the IRB, the risks reported in the literature, and the unapproved status of the product |
| 10. What evidence supports this for someone like me, and may I have the citations? | Clinics claimed good results in 82 percent of patients while the trial evidence is low certainty [11, 21] | Named trials or reviews with their follow-up points and their own certainty ratings, such as the 2021 knee review [21] |
| 11. What happens if something goes wrong, and how is it reported? | The FDA asks that adverse events go to MedWatch [1, 22] | A written adverse event procedure, the clinic’s MedWatch practice, and the lot number recorded in your chart |
| 12. What is the total cost in writing, and what does it include? | The mean quoted price was $5,156 per knee injection, and patients have crowdfunded these costs [11, 13] | An itemized written quote covering the product, the procedure, follow-up visits and imaging, before any deposit |
The product, the tissue bank and the registration number identify what is offered
The FDA keeps a public query of human cell and tissue establishments that can be searched by establishment name, by function such as recover, process, store or distribute, by product such as umbilical cord tissue, and by state [5]. An entry there shows that a firm has registered and listed its products under 21 CFR 1271.10, which is a duty placed on manufacturers of certain cell and tissue products [6].
That entry says nothing about approval. The CDC report on the 2018 infections states that although the processor and the distributor were registered with FDA, such registration is not a form of FDA approval, and the FDA patient page repeats the point [2, 18]. A registration number is the start of the paperwork a clinic should hold, and the certificate of analysis is the rest of it.
The FDA guidance for somatic cell products lists the final product tests: sterility, mycoplasma and adventitious agents, identity, purity including endotoxin, potency and viability, with viability generally at least 70 percent [23]. Identity for a mesenchymal cell product means the markers CD105, CD73 and CD90 present and CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR absent, and donor serology covers HIV, hepatitis B and C and syphilis for every donor [24, 26].
ExaVeyra supplies mesenchymal stem cells from an FDA-registered tissue bank that ships to all 50 states and Puerto Rico where state law permits the use, each vial carries its lot number, and a certificate of analysis exists for every lot, with serology. The certificate, the characterization panel and the cold-chain records are available on request to the practice, which can show them to a patient who asks question 6 and question 7.
Understanding what the evidence does not yet show
A documented answer to question 10 includes what the trials have not shown. The following gaps are as much a part of the evidence as the findings, and a clinic that states them is giving you a complete answer.
- Approval for any orthopedic, neurological, cardiovascular or pulmonary use, or for pain, which the FDA states no listed product has [1]
- High-certainty evidence of benefit: the 2021 knee review graded its 14 trials as low to very low certainty, with 10 at high risk of bias [21]
- Safety data for uncharacterized products, since the pooled safety record comes from registered trials with characterized cells [20]
- Outcomes beyond four years, the longest randomized follow-up in the knee literature [21]
- Any published basis for the 82 percent success figure clinics quoted to a simulated patient [11]
- Whether registration, a clinicaltrials.gov listing or a state statute changes the federal status of a product, which the FDA says they do not [2]
State law and the IND question decide whether the offer is lawful where you live
State law is the second layer of question 5. Florida’s statute, sections 458.3245 and 459.0127 as enacted by Senate Bill 1768 effective July 1, 2025, permits physicians to offer stem cell products in orthopedics, wound care and pain management from suppliers that hold FDA registration and accreditation by AABB, AATB, NMDP or WMDA, with written notice and signed consent. Georgia (O.C.G.A. 43-34-49, effective July 1, 2026), Tennessee (Public Chapter 1016, effective July 1, 2026), Nevada (NRS 629.300 to 629.390) and Utah (section 58-1-512, effective May 6, 2026) have enacted permission statutes with their own conditions.
Texas (Health and Safety Code chapter 1003 with Penal Code 48.04) and North Carolina (G.S. 90-325.15) make selling adult stem cells for investigational use a crime, and Texas Health and Safety Code 1003.002 limits adult stem cell use in health care to clinical trials approved by the FDA. The state guides on this site set out each statute with its primary source and access date, and the practitioner and their counsel decide what a practice may do under the law of its state.
None of those statutes changes federal status. Marks and Gottlieb, writing as FDA leadership in 2018, described a framework that pairs expedited pathways for products developed through trials with enforcement against products marketed outside them [16]. The ISSCR 2021 guidelines, written as a resource for physicians and patients, place interventions sold outside regulated trials outside the standard for clinical translation [15]. A state permission statute adds conditions for a physician and leaves the federal IND requirement in place [4].
The harms on record show what a missing answer costs
Kuriyan and colleagues described three patients whose acuity fell from 20/30 to 20/200 before to 20/200 to no light perception a year after bilateral intravitreal injections of their own adipose-derived cells at one US clinic [17]. There was no IND, no review board and no investigator’s brochure for a patient to ask about, which is the situation questions 3 and 9 are designed to surface.
The CDC documented 12 patients in three states hospitalized with bloodstream infections, joint infections or epidural abscesses in 2018 after a cord blood derived product in which unopened vials grew the same organisms, with contamination placed before distribution [18]. A lot-specific sterility result, question 6, is the document that was missing. Bauer and colleagues reviewed the wider case literature and found the serious events clustered outside regulated trials [19].
Please know that if you are being charged for these products or offered these products outside of a clinical trial, you are likely being deceived and offered a product illegally.
That sentence is the FDA’s, from its 2021 patient page [2]. The comparison point is what trial-grade evidence looks like: Thompson and colleagues pooled 55 randomized trials with 2,696 patients and found transient fever as the only excess event, and Wiggers and colleagues reported no serious adverse events over up to four years in 14 knee trials while grading the benefit evidence as low certainty [20, 21]. If you were harmed, the FDA asks you to report it to MedWatch, with the lot number if you have it [1, 22].
A printable checklist for the consultation
Print this list or save it to your phone. Ask the questions in order, and for each one write down the document you were shown or the reason you were not shown one. The FDA invites questions by phone at 800-835-4709 and by email at ocod@fda.hhs.gov if any answer leaves you unsure [1].
- What is the product, from which tissue, and whose cells are they?
- Which tissue bank or manufacturer made it, and what is its FDA registration number?
- Has the FDA reviewed it, and what is the IND number and sponsor?
- Is it FDA approved, and can you show me where it appears on the FDA list?
- What does my state’s law say, and may I see the written notice it requires?
- May I see the certificate of analysis for my lot?
- How was it shipped and stored, and may I see the temperature record?
- Who will perform the procedure, and what is their license and specialty?
- What does the consent form say, and which review board approved it?
- What evidence supports this for someone like me, and may I have the citations?
- What happens if something goes wrong, and how is it reported?
- What is the total cost in writing, and what does it include?
Documentation is how a practice answers all twelve questions
A practice that holds a verified account can answer questions 1, 2, 6 and 7 from its own files. Anyone may apply or ask the scientific team a question without an NPI, and NPI verification, which takes 1 to 3 business days, gives access to the practitioner portal, product documentation and pricing, where the certificate of analysis, the characterization panel and the cold-chain records for any lot can be requested.
For a patient, the checklist turns a sales conversation into a document review, and a practice that welcomes the review has already done most of the work. The FDA, the CDC and the peer-reviewed literature have made the questions clear, and the number of practices able to answer them with paperwork grows each year.
Aviso Educativo: This article is for educational purposes only and does not constitute medical or legal advice. It does not identify any material, compound, device setting or protocol as safe, effective or appropriate for any patient, and it is not intended to diagnose, treat, cure, or prevent any disease. Questions about a treatment belong with the reader’s own licensed provider. Exosome material is supplied for topical aesthetic use by licensed practitioners. No exosome product is FDA-approved for any use, and ExaVeyra Sciences makes no statement about administration, route, or outcome. Compounded medications are not FDA-approved. They are prepared by a 503A compounding pharmacy licensed by the Texas State Board of Pharmacy for an individual patient against that patient’s prescription, and are available to NPI-verified licensed practitioners only, in the states where the pharmacy is licensed. Product, device and brand names mentioned are trademarks of their respective owners and are used only to identify the products discussed. Their mention is not an endorsement, and those owners have not reviewed or endorsed this article. ExaVeyra Sciences is a supplier and takes no part in any diagnosis, treatment decision, or plan of care. Findings described are attributed to the peer-reviewed literature, trial registries and agencies cited. The content of these guides is provided for general informational purposes only. It does not constitute legal, medical, or regulatory advice, and does not establish that any particular product or practice is compliant. Regulatory requirements vary by state and depend on the circumstances of each practice. Each practitioner should consult their own legal counsel and the applicable state licensing boards before acting on anything stated here.
Referencias
- 1.U.S. Food and Drug Administration. Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. Dated July 22, 2020; content current as of April 9, 2024; verified 4 November 2026. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomesAgency consumer page. Carries in this article: stem cell products generally require FDA approval; the approved stem cell products consist of blood-forming stem cells derived from umbilical cord blood; none of the listed products have been approved for any orthopedic, neurological, cardiovascular or pulmonary condition, autism, macular degeneration, blindness, chronic pain or fatigue; the agency invites questions by phone (800-835-4709) and email (ocod@fda.hhs.gov); and adverse events go to MedWatch.
- 2.U.S. Food and Drug Administration. Important Patient and Consumer Information About Regenerative Medicine Therapies. Dated June 3, 2021; verified 4 November 2026. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapiesAgency consumer page. Carries in this article: the statement that a person charged for these products or offered them outside a clinical trial is likely being deceived and offered a product illegally; that inclusion in clinicaltrials.gov or registration with FDA does not mean a product is legally marketed; the list of reported safety concerns (blindness, tumor formation, neurological events, bacterial infections, site reactions, immune response, unintended tissue, cross-contamination); and the invitation to contact ocod@fda.hhs.gov.
- 3.U.S. Food and Drug Administration. Public Safety Notification on Exosome Products. December 6, 2019; verified 4 November 2026. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/public-safety-notification-exosome-productsAgency safety notification. Carries in this article: the agency advice to patients considering exosome products, which this article applies to cell products, namely to ask whether FDA has reviewed it, to ask the clinical investigator for the FDA-issued IND number and the chance to review the FDA communication acknowledging the IND, to sign a consent form that identifies the institutional review board, and to ask the sponsor for the investigator’s brochure; the same page states there are no FDA-approved exosome products.
- 4.U.S. Food and Drug Administration. Investigational New Drug (IND) Application. Verified 4 November 2026. https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-applicationAgency explainer. Carries in this article: federal law requires that a drug be the subject of an approved marketing application before it is transported or distributed across state lines, and the IND is the means through which a sponsor obtains an exemption from that requirement for a clinical study, the reason an IND number is the document that makes an investigational product lawful to ship.
- 5.U.S. Food and Drug Administration. Human Cell and Tissue Establishment Registration (HCTERS), Public Query. Verified 4 November 2026. https://www.accessdata.fda.gov/scripts/cber/CFAppsPub/tiss/index.cfmAgency database. Carries in this article: the public search of registered HCT/P establishments by establishment name, function (recover, screen, test, process, store, label, package, distribute), product (including umbilical cord tissue and HPC cord blood), status (registered, inactive, pre-registered) and state, the tool a patient or practice uses to check a tissue bank’s registration.
- 6.U.S. Food and Drug Administration. 21 CFR 1271.10, Are my HCT/Ps regulated solely under section 361 of the PHS Act and the regulations in this part, and if so what must I do? (66 FR 5466, 2001, as amended 2004; text verified on eCFR 4 November 2026). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1271.10 and https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271/subpart-A/section-1271.10Federal regulation. Carries in this article: the four cumulative criteria (minimal manipulation, homologous use, no combination with another article beyond the listed agents, and no systemic effect or dependence on living cells unless autologous, close-relative or reproductive) that place a product under section 361 alone, and the registration and listing duty that follows, which is what a registration number records.
- 7.Turner L. The American stem cell sell in 2021: U.S. businesses selling unlicensed and unproven stem cell interventions. Cell Stem Cell. 2021;28(11):1891-1895. PMID 34739831. doi:10.1016/j.stem.2021.10.008Systematic internet survey of US businesses marketing stem cell interventions, March 2021. Carries in this article: 1,480 businesses operating 2,754 clinics were selling stem cell products that are not FDA approved, more than four times the number found in 2016. Disclosure: none stated in the PubMed record.
- 8.Turner L, Knoepfler P. Selling Stem Cells in the USA: Assessing the Direct-to-Consumer Industry. Cell Stem Cell. 2016;19(2):154-157. PMID 27374789. doi:10.1016/j.stem.2016.06.007First systematic analysis of internet marketing by US stem cell businesses. Carries in this article: widespread promotion of unapproved interventions by businesses based in the United States, the baseline the 2021 survey is measured against. Disclosure: none stated in the PubMed record.
- 9.Knoepfler PS, Turner LG. The FDA and the US direct-to-consumer marketplace for stem cell interventions: a temporal analysis. Regen Med. 2018;13(1):19-27. PMID 29327974. doi:10.2217/rme-2017-0115Temporal analysis of US stem cell business websites against FDA enforcement activity. Carries in this article: new business websites at least doubled on average each year from 2009 to 2014 and appeared at about 90 to 100 per year from 2014 to 2016, while FDA warning letters over the same period were limited. Disclosure: none stated in the PubMed record.
- 10.Fu W, Smith C, Turner L, Fojtik J, Pacyna JE, Master Z. Characteristics and Scope of Training of Clinicians Participating in the US Direct-to-Consumer Marketplace for Unproven Stem Cell Interventions. JAMA. 2019;321(24):2463-2464. PMID 31237628. doi:10.1001/jama.2019.5837Research letter describing the credentials and scope of training of physician and nonphysician practitioners working for US companies that market unproven stem cell procedures. Carries in this article: the basis for asking who performs the procedure and in what specialty they trained. Disclosure: two authors were members of the Federation of State Medical Boards workgroup on regenerative and stem cell practices.
- 11.Piuzzi NS, Ng M, Chughtai M, Khlopas A, Ng K, Mont MA, et al. The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective. J Knee Surg. 2018;31(6):551-556. PMID 28738432. doi:10.1055/s-0037-1604443Prospective cross-sectional secret-shopper survey of 317 US centers marketing stem cell procedures for musculoskeletal conditions, 273 reached. Carries in this article: the mean quoted price of a same-day knee injection was $5,156 (standard deviation $2,446; 65 centers) and centers claimed a mean of 82 percent of patients had good results, against the published evidence the authors describe as low level. Disclosure: none.
- 12.Murdoch B, Zarzeczny A, Caulfield T. Exploiting science? A systematic analysis of complementary and alternative medicine clinic websites’ marketing of stem cell therapies. BMJ Open. 2018;8(2):e019414. PMID 29490963. doi:10.1136/bmjopen-2017-019414Systematic website analysis, global with a US and English-language bias; 243 websites offering stem cell interventions. Carries in this article: statements of general risks appeared on 24.69 percent of sites, risks specific to the mode of therapy on 5.76 percent, regulatory status on 30.86 percent, and the experimental or unproven nature on 33.33 percent. Disclosure: competing interests none declared.
- 13.Snyder J, Turner L, Crooks VA. Crowdfunding for Unproven Stem Cell-Based Interventions. JAMA. 2018;319(18):1935-1936. PMID 29801003. doi:10.1001/jama.2018.3057Research letter analyzing crowdfunding campaigns for unproven stem cell interventions. Carries in this article: the finding that patients raise money online to pay for these procedures, the reason the cost question belongs in writing before any commitment. Disclosure: none stated in the PubMed record.
- 14.Sipp D, Caulfield T, Kaye J, Barfoot J, Blackburn C, Chan S, et al. Marketing of unproven stem cell-based interventions: A call to action. Sci Transl Med. 2017;9(397):eaag0426. PMID 28679655. doi:10.1126/scitranslmed.aag0426Policy review by an international group. Carries in this article: the characterization of direct-to-consumer marketing of unproven stem cell interventions as a global problem resistant to regulatory efforts, and the call for engagement, harmonization and enforcement. Disclosure: non-US government research support listed in the PubMed record.
- 15.Lovell-Badge R, Anthony E, Barker RA, Bubela T, Brivanlou AH, Carpenter M, et al. ISSCR Guidelines for Stem Cell Research and Clinical Translation: The 2021 update. Stem Cell Reports. 2021;16(6):1398-1408. PMID 34048692. doi:10.1016/j.stemcr.2021.05.012Summary of the International Society for Stem Cell Research guidelines update. Carries in this article: the guidelines serve as a resource for physicians and members of the public including patients, and they place unproven interventions sold outside regulated trials outside the standard for clinical translation. Disclosure: an extensive declaration of interests accompanies the paper; the chair declares no financial conflicts.
- 16.Marks P, Gottlieb S. Balancing Safety and Innovation for Cell-Based Regenerative Medicine. N Engl J Med. 2018;378(10):954-959. PMID 29514023. doi:10.1056/NEJMsr1715626Special report by the director of the FDA biologics center and the FDA commissioner. Carries in this article: the agency framework for regenerative medicine, which pairs expedited pathways for products developed through trials with enforcement against products marketed outside them. Agency authors.
- 17.Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE 2nd, et al. Vision Loss after Intravitreal Injection of Autologous "Stem Cells" for AMD. N Engl J Med. 2017;376(11):1047-1053. PMID 28296617. doi:10.1056/NEJMoa1609583Case series of three patients evaluated after bilateral intravitreal injection of autologous adipose-derived cells at one US clinic. Carries in this article: acuity before the injections of 20/30 to 20/200 and at one year of 20/200 to no light perception, the clearest documented cost of a procedure done outside an IND. Disclosure: none stated in the PubMed record.
- 18.Perkins KM, Spoto S, Rankin DA, Dotson NQ, Malarkey M, Mendoza M, 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;67(50):1397-1399. PMID 30571672. doi:10.15585/mmwr.mm6750a5. Verified 4 November 2026 at https://www.cdc.gov/mmwr/volumes/67/wr/mm6750a5.htmCDC field report of a multistate investigation. Carries in this article: 12 patients in Texas, Florida and Arizona were hospitalized with bloodstream infections, joint infections or epidural abscesses after a cord blood derived product, unopened vials grew the same organisms, contamination was placed before distribution, and the report states that FDA registration is not a form of FDA approval. Disclosure: no potential conflicts reported.
- 19.Bauer G, Elsallab M, Abou-El-Enein M. Concise Review: A Comprehensive Analysis of Reported Adverse Events in Patients Receiving Unproven Stem Cell-Based Interventions. Stem Cells Transl Med. 2018;7(9):676-685. PMID 30063299. doi:10.1002/sctm.17-0282Review of scientific publications, case reports and media reports of safety incidents after unproven stem cell interventions. Carries in this article: the serious reported events cluster in settings outside regulated trials, and providers often take advantage of a willingness to pay large sums. Disclosure: none stated in the PubMed record.
- 20.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. PMID 31989101. doi:10.1016/j.eclinm.2019.100249Systematic review and meta-analysis of randomized controlled trials of intravascular MSCs in adults; 55 trials, 2,696 patients. Carries in this article: in registered trials with characterized products, transient fever was the only excess event, the comparison point for any safety claim a clinic makes. Funding: Stem Cell Network, Ontario Institute for Regenerative Medicine and Ontario Research Fund; two authors report affiliations with Northern Therapeutics.
- 21.Wiggers TG, Winters M, Van den Boom NA, Haisma HJ, Moen MH. Autologous stem cell therapy in knee osteoarthritis: a systematic review of randomised controlled trials. Br J Sports Med. 2021;55(20):1161-1169. PMID 34039582. doi:10.1136/bjsports-2020-103671Systematic review of 14 randomized trials, 408 patients, with ROB 2 and GRADE. Carries in this article: 19 of 26 outcome measures improved at one year, no serious adverse events over up to four years, 10 of 14 trials at high risk of bias, and low to very low certainty, which is what a documented answer to the evidence question looks like. Disclosure: competing interests none declared.
- 22.U.S. Food and Drug Administration. MedWatch: The FDA Safety Information and Adverse Event Reporting Program. Content current as of November 3, 2026; verified 4 November 2026. https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-programAgency reporting program page. Carries in this article: MedWatch is the FDA medical product safety reporting program for health professionals, patients and consumers, and it receives reports on biologics including human cells and tissue transplants.
- 23.U.S. Food and Drug Administration, Center for Biologics Evaluation and Research. Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs). Guidance for FDA Reviewers and Sponsors, April 2008, docket FDA-2008-D-0206; page and PDF verified 4 November 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-and-review-chemistry-manufacturing-and-control-cmc-information-human-somatic-cell-therapy and https://www.fda.gov/media/73624/downloadAgency guidance. Carries in this article: the final product testing headings for a cell product, namely sterility, mycoplasma and adventitious agents, identity, purity including endotoxin, potency and viability, with a minimum viability specification generally set at 70 percent, the list a certificate of analysis is read against.
- 24.U.S. Food and Drug Administration. 21 CFR 1271.85, What donor testing is required for different types of cells and tissues? (text verified on eCFR 4 November 2026). https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=1271.85 and https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part-1271/subpart-C/section-1271.85Federal regulation, donor eligibility. Carries in this article: every donor is tested for HIV types 1 and 2, hepatitis B, hepatitis C and syphilis, and donors of viable leukocyte-rich tissue also for HTLV types I and II and cytomegalovirus, the serology panel a lot record should show.
- 25.U.S. Food and Drug Administration. FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease. Press release, December 18, 2024; verified 4 November 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host. Listed on Approved Cellular and Gene Therapy Products, content current as of October 30, 2026. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-productsAgency press release and licensed product list. Carries in this article: Ryoncil (remestemcel-L-rknd), an allogeneic bone marrow derived MSC product for pediatric steroid-refractory acute graft-versus-host disease, approved December 18, 2024, is the only approved MSC product, so a clinic that calls any other stem cell product FDA approved is making a claim the agency list does not support.
- 26.Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-317. PMID 16923606. doi:10.1080/14653240600855905Society position statement. Carries in this article: the identity markers an MSC lot is read against, namely CD105, CD73 and CD90 present and CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR absent, so a certificate that names no markers has not shown what the product is.