What are the side effects of stem cell therapy? Mostly mild in small trials

The side effects of stem cell therapy recorded in trials are mostly mild, and they pass. The largest pooled safety record available is 11 trials in 461 patients treated for autism spectrum disorder, with no serious adverse events attributed to the treatment [3]. The events logged most often in those trials were:

• fever
• hyperactivity
• vomiting
• headache
• aggressive behaviour

Serious events do occur. A randomised trial infused allogeneic cells, meaning cells from a donor rather than from the patient, into 37 people with mild Alzheimer's disease, and gave 12 others a placebo drip. One person in each of the three treated groups had a serious medical event within four weeks of an infusion, and none of the 12 on placebo did [1]. With 11 to 13 people per group that is a single event each, and there was no sign of more events in the group given four times as many cells. Nobody reacted to the infusion itself and nobody had an allergic reaction [1].

Injections into a joint look much the same. Thirty people with knee osteoarthritis were randomised either to injections of cells taken from their own fat or to carrying on with usual care, and no serious adverse events were recorded over 12 months [5]. A 2023 review of 22 studies, 21 of them clinical trials, in people with traumatic spinal cord injury found no significant adverse events over the short and medium term, while warning that the evidence is too thin to generalise from and that long-term safety is unknown [2].

On the risk of cancer, the longest controlled follow-up available tracked 219 people with advanced liver scarring caused by hepatitis B. The 108 who received three infusions of umbilical-cord cells four weeks apart were followed for between 13 and 75 months, with no significant side effects or treatment-related complications, and liver cancer appeared about as often in the treated group as in the untreated one [6].

The alarming numbers attached to this subject describe a different procedure. Among 3,552 people with the blood cancer multiple myeloma who had their own blood-forming stem cells returned after chemotherapy, 45.7% had a complication within the first 100 days, infections twice as often as everything else combined, after which the rate dropped sharply [14]. In a smaller group of 33 patients given cells from a donor instead, 30% developed acute graft-versus-host disease, which is the donor immune system attacking the recipient's own tissue, and 61% the chronic form. Three in every 100 died of something other than their cancer returning within 100 days, rising to 24 in every 100 by five years [12].

Whether stem cell therapy is safe depends on which of two procedures is meant, because they do opposite things to the body. Mesenchymal stem cells, the connective-tissue cells harvested from fat, bone marrow or donated umbilical cord, are injected into a joint or dripped into a vein, and are not meant to replace the tissue they land in. What the trials watched for was an immediate reaction to the product, and the infusion trial found none: no reaction to the infusion, no allergic reaction [1]. Three courses of donor-derived infusions in people with liver cirrhosis produced no complications the investigators attributed to the treatment either [6].

A bone marrow transplant does the opposite. Blood-forming stem cells are given to rebuild the marrow, which has to be emptied with chemotherapy first, and when the cells come from a donor the new immune system can read the recipient's own tissue as foreign. That is graft-versus-host disease, and it appeared in acute form in 30% and chronic form in 61% of those 33 transplanted patients [12].

One trial pulls those two sources of harm apart. Eighteen patients with severe beta-thalassaemia, an inherited blood disorder that otherwise requires lifelong transfusions, were given their own gene-corrected blood stem cells after marrow-clearing chemotherapy. Every one of them had at least one adverse event, no serious one was judged related to the cell product itself, and nobody died [10]. The danger in those procedures sits in the chemotherapy and the donor mismatch rather than in the cells.

Cancer is the hardest question to settle, because cells that can divide could in principle form a growth, and checking means waiting. Over up to just over six years of controlled follow-up, liver cancer was no more common among people who had been infused than among those who had not [6]. Transplant specialists still recommend years of follow-up for people cured of a blood cancer, because late cancers and other late complications take that long to show up [15].

The numbers come from small trials. The dose-finding infusion trial involved 49 people split into four groups of 11 to 13 [1], and the knee trial 30 people [5]. A side effect that affects one person in 500 is invisible at that size, so "no serious adverse events" means nobody in these trials had one, which is not the same as nobody having one.

Follow-up is short. The infusion trial reported at 39 weeks [1], the knee trial at 12 months [5], and only the liver study ran past five years [6]. Nothing here says what happens after a decade.

The evidence does not apply to:

• healthy adults buying an infusion for ageing, energy or recovery, since none of these trials enrolled anyone like that and there is no controlled safety record for that use
• anyone reading the transplant figures as a guide, because those patients had blood cancers and chemotherapy [12][14]
• people given exosome products, which are not cells at all and were not tested in any of these trials
• conditions other than the ones studied here, which were Alzheimer's disease [1], spinal cord injury [2], autism [3], knee osteoarthritis [5] and liver cirrhosis [6]

Trial products are prepared under study conditions and given in monitored settings. A preparation made up in a commercial clinic is not the same product, so none of this safety record transfers to any particular provider. The spinal cord injury reviewers made that caution explicit about their own findings [2].

None of this is about whether stem cell therapy works, only about what the trials recorded happening to the people in them.

Longevity and regenerative clinics sell this service, and a first visit is usually a consultation rather than a procedure: a history, imaging of the painful joint if that is the complaint, and a price. The procedure itself means either harvesting cells from your own fat or bone marrow and processing them in the same session, or buying in a donor-derived product, and the injection may or may not be placed under ultrasound guidance. The questions that tell one clinic from another are factual ones: what exactly is being injected, whether the regulator has approved it for the purpose proposed, who performs the injection, and what a single treatment costs. None of the trials above tested a clinic's own preparation, which is why their safety record cannot be read as a safety record for the service you are quoted for.