Longevity Science • Category 15 · New

How to identify a safe regenerative medicine clinic.

Regenerative medicine — mesenchymal stem cells, exosomes, advanced PRP — is growing faster than regulation. In that gap, pharmaceutical-grade laboratories coexist with operations applying products with no traceability. The patient should not have to guess. These are the 7 minimum criteria the International Society for Cell & Gene Therapy (ISCT), the International Society for Stem Cell Research (ISSCR), the FDA under 21 CFR 1271 and the EMA under the ATMP framework require — and every responsible clinic should meet before applying a biological product to a human being.

Regulation moves slower than the market. The patient is caught in between.

Regenerative medicine advances globally at a pace no national regulatory framework can match. The United States (under 21 CFR 1271 and the FD&C Act), the European Union (under the ATMP framework), Japan (PMD Act), Australia (TGA), and Iglesias-López et al. (Front Pharmacol 2019) have documented the asymmetry: advanced therapy offerings grow faster than agencies' audit capacity. In that gap, the patient is caught — between serious GMP-documented laboratories and operations promising "stem cells" without minimum quality testing.

What follows is the international consensus translated into askable language — seven concrete questions any patient can ask before accepting a procedure. If a clinic does not answer them with objective documentation, that is an answer in itself. Marks, Witten and Califf — from the FDA CBER leadership — stated in NEJM (2017): "transparency about evidence and processes is not optional in cell therapy; it is the minimum safety line".

One of the most commonly offered indications in regenerative medicine is chronic joint pain — and precisely for that reason it is one of the scenarios where demanding documentation matters most. The decision to apply stem cells or exosomes into a joint should be preceded not only by these 7 product-quality criteria, but also by a broad evaluation of the patient's biological context: biological age, inflammatory profile, body composition, hormonal profile.

"Transparency about evidence and processes is not optional in cell therapy; it is the minimum safety line." — Marks, Witten, Califf · NEJM 2017
Ch. 02 · The 7 minimum safety criteria

The seven criteria every clinic must be able to document — with paper and signature

Each one derives from international consensus: ISCT (Dominici 2006, Krampera 2013, Galipeau 2016), ISSCR Guidelines 2016 (Daley et al.), FDA 21 CFR 1271, EMA ATMP, and standards from the United States Pharmacopeia (USP <71>, <63>, <85>). They are not opinions — they are the published minimum criteria.

  • 01 · Cell or exosome origin

    Source documentation

    Where do they come from? Umbilical cord, bone marrow, adipose tissue, placenta? How was the donor selected — medical history, family history, risk factors? What infectious testing was performed — HIV-1/2, HBsAg, anti-HBc, anti-HCV, HTLV-I/II, VDRL, CMV, context-specific Zika, Chagas, tuberculosis? FDA under 21 CFR 1271 requires documentation of each.

  • 02 · Sterility testing

    USP <71> · USP <63>

    Mandatory tests: bacteria and fungi (USP <71> — Sterility Tests, direct or filtration method), Mycoplasma (USP <63> — Mycoplasma Tests, culture or NAT), and endotoxins (USP <85> — Bacterial Endotoxins Test). The source laboratory must certify per-lot results. A positive Mycoplasma is not just an "infection" — it is a contaminant invisible to ordinary controls that alters cell function.

  • 03 · Cell viability

    % live cells per dose

    How many live cells does the product contain? The market minimum for MSC is ≥70% viability at dosing (trypan blue staining, 7-AAD exclusion flow cytometry, or annexin V). The CoA must declare total count and viable count. Applying a product without knowing how many viable cells it contains is applying volume, not therapy.

  • 04 · Biological potency

    Demonstrated functionality

    Galipeau et al. (Cytotherapy 2016) proposed immune functional assays as the potency release criterion for MSC: suppression of activated T-cell proliferation, M2 macrophage polarization, IDO, PGE2, TGF-β secretion. Without potency testing, a clinic applies millions of technically alive cells with no real functional capacity. Alive ≠ functional.

  • 05 · Traceability

    Lot · date · chain of custody

    Every biological product applied must be traceable from origin to dose: lot number, production date, expiration date, transport (cold chain), in-clinic storage, and documented chain of custody. This enables adverse event investigation, contaminated lot recall, and regulatory audit. Without traceability, no legal accountability exists from the source laboratory.

  • 06 · Clinical follow-up

    Protocolized 24h → 12 months

    The international standard (ISSCR Guidelines 2016) proposes structured follow-up: short-term (24h, 72h, 7 days) for immediate adverse surveillance; intermediate (1, 3, 6 months) with clinical and biomarker re-evaluation; long-term (12 months minimum) for sustained response and deferred adverse events. Absence of follow-up prevents objectifying response and detecting deferred adverse events.

  • 07 · Patient selection

    Written inclusion/exclusion criteria

    Bauer et al. (Stem Cells Transl Med 2018) systematically reviewed adverse events in patients receiving unapproved interventions — a significant proportion occurred in inappropriate candidates. Typical exclusion criteria: active cancer, active infection, pregnancy, decompensated autoimmunity, coagulopathy, severe cardiovascular comorbidity. A serious clinic has written protocol and says "no" when "no" is the correct answer.

What the international standard requires · what the average clinic does · what we do at Wellness Care

The following comparison does not attack anyone in particular. It documents — honestly — the average gap between what the international standard requires and what the market generally delivers. And it declares, in the third column, how Wellness Care responds to each criterion. The patient can use this framework to evaluate any offer — including ours. That is the point.

Criterion What the international standard requires Average clinic Wellness Care
Product Certificate of Analysis (CoA) Documented per lot — viability, sterility, Mycoplasma, endotoxins, ISCT flow cytometry. Not always available to the patient. Delivered to the patient before each procedure.
Pre-procedure functional evaluation Complete medical history + objective biomarkers + written criteria. Variable — depends on the operator. Written inclusion/exclusion protocol with objective biomarkers.
Post-procedure clinical follow-up 24h, 72h, 1m, 3m, 6m, 12m with re-measurement. Limited to the immediate post-procedure visit. Protocolized calendar through 12 months with biomarker re-measurement.
Inflammatory and immune biomarkers hsCRP, IL-6, ESR, autoimmune profile as minimum. Rarely requested before the procedure. Inflammatory + autoimmune panel mandatory at initial evaluation.
Integrated functional medicine Recommended to identify root cause before regeneration. Rarely integrated into the protocol. Functional + bioregulatory evaluation integrated into the protocol.
Product lot traceability Documented as standard — lot, date, chain of custody. Variable — depends on the source laboratory. Complete traceability by lot, date and chain of custody.
Written patient selection protocol Written inclusion/exclusion criteria with medical signature. Variable — not always formalized. Written protocol signed by medical direction.

Framework based on: ISCT (Dominici 2006, Galipeau 2016) · ISSCR Guidelines 2016 (Daley et al.) · FDA 21 CFR 1271 · EMA ATMP · USP <71> <63> <85>

"A clinic that does not show the CoA is not protecting the laboratory. It is protecting something else."

I am a bacteriologist. I learned sample quality and chain of custody before longevity medicine. That is why, the day we decided to incorporate regenerative medicine at Wellness Care, the first thing we negotiated with supplier laboratories was access to the Certificate of Analysis — viability, sterility, Mycoplasma, endotoxins, ISCT flow cytometry — per lot, on every dose, without exception. If the laboratory could not provide that systematically, it was not a supplier.

This page exists because the patient should not have to learn bacteriology to protect themselves. They should be able to ask for a document and understand what it says. And if the clinic does not have it, that too is an answer. Responsible regenerative medicine is transparent about its evidence and its limits. Irresponsible regenerative medicine is not.

A serious clinic says "no" when "no" is the right answer. And it shows the document when the document should be shown.
Ch. 05 · International regulatory framework

The five authorities defining the global standard of regenerative medicine

The criteria above are not editorial invention — they are consensus from the global authorities regulating cell and advanced therapies. It helps to know who is who, what they publish, and how to invoke them when evaluating a clinical offer.

  • ISCT

    International Society for Cell & Gene Therapy

    The international scientific society defining minimum criteria for characterizing MSC (Dominici 2006), functional potency criteria (Galipeau 2016), and immunocharacterization (Krampera 2013). Its position papers are the most-cited reference for cell quality in the literature.

  • ISSCR

    International Society for Stem Cell Research

    Publishes the Guidelines for Stem Cell Research and Clinical Translation (Daley et al. 2016). Defines ethics, clinical translation, patient communication, post-procedure follow-up, and handling of preliminary evidence.

  • FDA 21 CFR 1271

    Food and Drug Administration · US

    US federal regulation on human cellular and tissue-based products (HCT/P). Defines donor, manufacturing, labeling, and traceability obligations. Marks, Witten and Califf (CBER FDA, NEJM 2017) clarified its application to cell therapy.

  • EMA ATMP

    European Medicines Agency · ATMP framework

    European framework for Advanced Therapy Medicinal Products. Iglesias-López et al. (Front Pharmacol 2019) reviewed the FDA comparison. Applies to somatic cell therapies, gene therapies, and tissue-engineered products. Reference standard for Latin America importing European therapy.

  • INVIMA Colombia

    National Drug and Food Surveillance Institute

    Colombian regulatory authority. Mesenchymal stem cell therapies, exosomes, and therapeutic peptides are not approved by INVIMA for commercial use at the time of this publication. Any clinical discussion of these modalities in Colombia is educational, individualized, and within the compassionate use framework.

The seven questions any patient can ask before accepting a procedure

Whether a clinic responds with objective documentation — or sidesteps the questions — is clinically relevant information. These are the seven questions, in askable language. They work for evaluating any regenerative medicine offer, including ours at Wellness Care.

  1. What source do the cells or exosomes I will receive come from? Ask for the laboratory name, tissue type, donor selection criteria.
  2. May I see the Certificate of Analysis (CoA) for the lot assigned to me? It should include viability, sterility, Mycoplasma, endotoxins, flow cytometry.
  3. How many viable cells does the dose contain and by what method was it quantified? Total count, % viability, exclusion technique.
  4. How is the biological potency of the product demonstrated? Functional assays, not just count or morphology.
  5. What is the lot number, production date, and chain of custody? Traceable and verifiable information.
  6. What clinical follow-up is protocolized after the procedure? Written calendar at 24h, 72h, 1m, 3m, 6m, 12m.
  7. What are the inclusion and exclusion criteria under which I am considered a candidate? Written protocol signed by medical direction.
If a clinic answers all seven with documents, it is within the standard. If it doesn't, that is also an answer.
Conclusion

Safe regenerative medicine is not measured by who promises it with the most enthusiasm. It is measured by who backs it with verifiable documentation — origin, sterility, viability, potency, traceability, follow-up, selection.

At Wellness Care we decided years ago that this would be the floor — not the ceiling. Transparency is not a gesture; it is a condition. And the best way to protect it is for the patient to know exactly what to ask. That is why this page exists.

Frequently asked questions about safety and quality in regenerative medicine

The most common questions about Certificates of Analysis, functional assays, traceability, patient selection, and regulatory framework. Each answer aligns with indexed literature: Marks 2017 (NEJM), Daley 2016 (Stem Cell Reports), Galipeau 2016 (Cytotherapy), Bauer 2018 (Stem Cells Transl Med), Krampera 2013 (Cytotherapy).

01

Why do I need a Certificate of Analysis (CoA) for the cell product?

The Certificate of Analysis (CoA) is the document proving the cell product passed pharmaceutical quality testing before application. It includes lot number, production date, viable cell count, sterility testing (USP <71>), Mycoplasma testing (USP <63>), endotoxins (USP <85>), and flow-cytometry characterization per ISCT criteria (CD73+, CD90+, CD105+ ≥95%; CD45−, CD34−, CD14−, CD11b−, CD79α−, CD19−, HLA-DR− ≤2%).

Without a documented CoA, the patient is accepting a biological product without objective evidence of its quality.

Dominici et al. · Cytotherapy · 2006 (ISCT criteria)
02

What are the 7 minimum criteria every clinic must meet?

The 7 criteria come from international consensus ISCT + ISSCR + FDA + EMA:

(1) Documented origin of cells or exosomes; (2) Sterility testing (bacteria, fungi, Mycoplasma, endotoxins); (3) Quantified cell viability; (4) Demonstrated biological potency; (5) Traceability (lot, date, chain of custody); (6) Protocolized clinical follow-up; (7) Rigorous patient selection with written criteria.

ISCT · ISSCR · FDA 21 CFR 1271 · EMA ATMP
03

What infectious tests are performed on the cell/tissue donor?

Minimum tests required by FDA under 21 CFR 1271 and EMA under the ATMP framework include:

HIV-1 and HIV-2, hepatitis B (HBsAg, anti-HBc), hepatitis C (anti-HCV), HTLV-I/II, syphilis (VDRL/RPR), CMV, and depending on epidemiological context, West Nile virus, Zika, Chagas, and tuberculosis.

Donor selection must be documented — structured medical history, family history, risk factors. For umbilical cord and placenta, the mother is additionally evaluated prenatally, with HLA typing when applicable.

04

What does biological potency mean and why does it matter?

Biological potency is the objective demonstration that the cells in the product maintain functional activity — not only that they are alive.

Galipeau et al. (Cytotherapy 2016) proposed immune functional assays as the potency release criterion: MSC capacity to suppress activated T-lymphocyte proliferation, polarize macrophages toward M2 phenotype, secrete IDO, PGE2, TGF-β.

Without potency testing, a clinic may apply millions of technically alive cells with no real functional capacity. The difference between both scenarios is absolute.

Galipeau et al. · Cytotherapy · 2016
05

What is lot traceability and why should I ask for it?

Traceability means every biological product applied can be traced from origin — donor, tissue, procurement date — to the administered dose — lot, production date, expiration date, transport, storage.

The chain of custody documents every transfer between laboratory, transporter and clinic. This enables adverse event investigation, contaminated lot recall, and regulatory audit compliance.

Without documented traceability, no legal accountability exists from the source laboratory.

06

Are all patients candidates for cell therapy?

No. Patient selection is one of the most critical criteria.

Bauer et al. (Stem Cells Translational Medicine 2018) systematically reviewed reported adverse events in patients receiving unapproved cell-based interventions — a significant proportion involved scenarios where the patient was not an appropriate candidate: active cancer, active infection, pregnancy, decompensated autoimmunity, coagulopathy, severe cardiovascular comorbidity.

A serious clinic has a written protocol of inclusion and exclusion criteria — and says "no" when "no" is the right answer.

Bauer et al. · Stem Cells Transl Med · 2018
07

What clinical follow-up should I expect after a regenerative procedure?

The international standard (ISSCR Guidelines 2016, Daley et al.) proposes:

(a) Short-term — 24h, 72h, 7 days — for immediate adverse event surveillance.
(b) Intermediate — 1, 3, 6 months — with clinical and objective biomarker re-evaluation.
(c) Long-term — 12 months minimum — to evaluate sustained response, deferred adverse events and re-treatment need.

Absence of systematic follow-up prevents objectifying response and detecting deferred adverse events. It is one of the most common market deficits.

Daley et al. · Stem Cell Reports · 2016 (ISSCR)
08

How does Wellness Care guarantee these 7 criteria?

Wellness Care does not produce cells or exosomes on-site — they are received from reference laboratories with documented Good Manufacturing Practice (GMP), pharmaceutical quality certification, and complete per-lot traceability.

Each patient receives the CoA of the product to be applied — viability, sterility, Mycoplasma, endotoxins, ISCT flow cytometry.

Patient selection involves complete medical history, advanced biomarkers (inflammation, autoimmunity, metabolic profile, hormonal) and written inclusion/exclusion criteria.

Clinical follow-up is protocolized at 24h, 72h, 1 month, 3 months, 6 months and 12 months with objective biomarker re-measurement.

About to receive cell therapy at another clinic?

Ask for your Certificate of Analysis before accepting

If you are about to receive stem cells or exosomes — at Wellness Care or at any other clinic — ask for the CoA of the lot assigned to you. A serious clinic will have it. If they do not, that is also clinically relevant information. If you have questions about how to read a CoA or want to talk to a team that practices under these criteria, book an educational evaluation.

Talk to the medical team