What the cells are thought to do, what a course of treatment involves, and what the evidence does and does not establish about the result.
What the Cells Are Thought to Do
For years the assumption was that injected cells become the missing tissue. The field's current account is different, and better supported.
Signalling
MSCs secrete a broad range of bioactive molecules — growth factors, cytokines and extracellular vesicles — collectively the secretome [7], and their isolation and characterisation follow established laboratory methods [6]. Caplan and Correa's framing of the cell as an "injury drugstore" [1]captures the mechanism: the cell arrives at a site of injury, senses the local environment, and releases what that environment calls for.
Immunomodulation
MSCs interact with both innate and adaptive immunity, generally dampening inflammatory responses [9]. ⚠️ Note the direction: this is immunosuppression, and it is why the one fully approved MSC therapy is for graft-versus-host disease. Interestingly, this effect does not depend entirely on the cells being alive — apoptotic and even dead MSCs retain immunomodulatory activity [9], which is difficult to reconcile with any account based on the cells becoming new tissue.
Homing
Infused cells distribute to sites of inflammation and injury. ⚠️ Route matters considerably here: intravascular delivery involves first-pass retention and interactions with blood that are specific to that route, and the field has called for clinical guidelines that reflect it [15].
What persistence looks like
Transplanted MSCs do not remain long. The honest statement of the model is that paracrine activity continues even as the cells themselves decline — and that this is the explanation for effects outlasting the cells rather than a problem for it [1][10].
⚠️ A mechanism is not an outcome. Everything above describes what the cells are thought to do. Whether that produces a clinical benefit for a given person, in a given condition, is a separate question answered only by trials — and the trials are covered below at their real strength.
On the name: the ISCT defines these cells as multipotent mesenchymal stromal cells [5], and Caplan — who coined "mesenchymal stem cell" — has argued the term should be medicinal signalling cells. Both come from the field's own authorities, and both point at signalling rather than replacement.
What a Course of Treatment Involves
Before arrival. Medical history, imaging review where relevant, and a candid conversation about whether treatment is appropriate at all.
Day 1 — assessment and preparation. Blood panels and baseline measures. Some protocols include NAD+ and exosome infusions on this day. ⚠️ These are preparatory components of the programme, not treatments with demonstrated clinical benefit in this context; NAD+ biology in ageing and metabolism is an active research area [3], and that is a different claim from a demonstrated effect on treatment outcome.
Day 2 — cell administration. Up to 100 million umbilical cord-derived MSCs, given as 50 million per session. ⚠️ On dose: the phase II frailty trial found physical performance improved in the 100-million group and not in the 200-million group [2]. More is not straightforwardly better, and cell counts should be understood as a product specification rather than a measure of expected benefit.
Days 3–7 — monitoring and support. Observation, supportive therapies, recovery.
Afterwards. Follow-up at intervals. ⚠️ Trials measure outcomes at fixed timepoints — typically 3, 6 and 9 months — and in the largest frailty trial the 6-month result was not statistically significant while the 9-month one was. Any timeline promising a particular experience at a particular week is not derived from trial data.
What the Evidence Establishes
⭐ Safety — the strongest evidence on this page
A multi-centre analysis of adverse events across 2,372 adult patients undergoing autologous stem cell therapy for orthopaedic conditions [14]is the largest real-world safety dataset available for this kind of treatment.
A systematic review and meta-analysis of MSC clinical trials (SafeCell) found no association between MSC administration and acute infusional toxicity, organ system complications, infection, death or malignancy, with transient fever the one identified signal [4].
Together these are a reasonable safety record — and a reasonable safety record is not evidence of benefit. They also do not address long-term outcomes, repeat dosing, or use in healthy people.
Efficacy — real, narrow, and honestly bounded
Knee osteoarthritis is the best-studied indication. A comprehensive appraisal of 15 randomised controlled trials and 11 non-randomised trials [16]found function improved in 12 of 15 RCTs versus baseline and 11 of 15 versus control, with cartilage protection or repair in 18 of 21 clinical studies — ⚠️ across a total of 610 patients, which its authors state is too few for definitive conclusions.
Individual trials include a phase I dose-escalation study of adipose-derived MSCs in severe knee OA [11], a proof-of-concept trial of intra-articular MSCs [13], and long-term follow-up of autologous MSCs in knee, ankle and hip OA [12].
Which cell source? A network meta-analysis of 15 studies and 585 patients [17]concluded that "MSCs transplantation effectively treats KOA patients, with autologous BM-MSC potentially offering more excellent benefits." ⚠️ Both clauses matter — the therapy works, and the source that performed best was autologous bone marrow.
Frailty. A randomised, double-blind, placebo-controlled phase II trial in 30 patients, all with diagnosed frailty [2]. ⚠️ No trial has studied this therapy in healthy people.
What is not established
Durability beyond trial windows · the optimal dose · the best cell source · whether structural disease modification occurs · any outcome in healthy people.
⚠️ The field's own assessment is candid about this. A review from within it is titled "Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities" [8]— and the challenges are given equal billing for a reason.
What Outcomes Look Like
Responses vary widely, and we cannot predict where any individual will fall.
Some people improve substantially. Most who improve do so meaningfully rather than dramatically. Some notice little or no change. ⚠️ We do not publish a response distribution, because we do not have controlled data to support one — and a percentage without a denominator, a definition and a control group is not a finding.
What does appear to influence response, from the trial literature [16]:
⚠️ *A note on what is not in that table. You will see it claimed that healthier patients respond better. No trial has compared response between healthier and less healthy recipients.* Disease severity predicting response is a finding among people who all have the disease; it is not the same claim, and the second one has never been tested.
We would rather say that than offer an explanation that would let us attribute a poor result to the patient.
Risks and Limitations
Reported effects are typically mild and short-lived: transient fever, fatigue, headache, injection-site or infusion reactions [4][14].
What is less well characterised: long-term outcomes; repeat-dosing safety, given that MSCs are immune evasive rather than immune privileged; and route-specific considerations for intravascular delivery [15].
Regulatory position. MSC therapy is not FDA-approved for orthopaedic, respiratory, autoimmune or anti-ageing indications. ⚠️ Availability in a permissive jurisdiction is not approval.
Not appropriate for: active malignancy · active infection · pregnancy · significant immunosuppression · anyone who has not discussed this with their own physician.
Frequently Asked Questions
Will the cells become my cartilage?
Probably not, and that is not how the benefit is currently thought to arise. Transplanted cells do not persist long; the account is that they signal to cells already present [1][10].
How long until I know if it worked?
Trials measure at 3, 6 and 9 months. Any more specific timeline is not derived from trial data.
Is more cells better?
Not on the available evidence. The phase II frailty trial found the 100-million group improved on physical performance and the 200-million group did not [2].
Should I have this instead of surgery?
⚠️ That is a question for your surgeon, and the honest answer is that they are not comparable on evidence. Joint replacement has among the best long-term outcome data in orthopaedics. What we can tell you is what this therapy's own evidence shows — a reasonable short-term safety record across 2,372 patients [14], and symptomatic benefit in knee osteoarthritis across multiple randomised trials on a total of 610 patients [16]. Decide on that, not on a comparison we are not positioned to make fairly.
I'm healthy — is this for me?
No trial has studied this therapy in healthy people. Anything offered on that basis is an extrapolation and should be described as one.
The Bottom Line
The mechanism — signalling rather than replacement — is well described and increasingly well supported. The safety record across thousands of patients is reasonable. The efficacy evidence is real, narrow, and concentrated in knee osteoarthritis on a small total number of patients.
Anyone who can tell you in advance how you will respond is telling you something the evidence does not contain.