Safety

Adverse Events (AEs)

Demonstrating safety and tolerability is the first stage in clinical research and is of the upmost importance. All treatment interventions used in clinical studies have the potential to cause side effects. In studies investigating stem cell therapy, safety and tolerability is often determined by assessing changes in vital signs, laboratory tests, physical examination, questionnaires, imaging studies and reported side effects, also known as adverse events (AEs). An AE as is defined by the FDA as “any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related”. AEs are classified depending on their seriousness, severity, expectedness and relatedness to the treatment. General categories include, serious or non-serious; expected or unexpected; not treatment related, possibly treatment related, and treatment related. A grading system of AEs has been developed and is used to report severity of AEs. There are 5 grades; Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening or disabling, Grade 5 is death. Most clinical trials often report only grade 3-5 AEs as these are most concerning. Grades 4 and 5 are considered to be serious adverse events (SAEs). An SAE is defined as “any untoward medical occurrence that at any dose results in death, hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity or congenial anomaly or birth defect.”

Reported Cases of Adverse Events

In 2018 Bauer et al presented a review of 35 cases describing acute or chronic complications or death after stem cell therapy. They used Google scholar and PubMed search engines and identified 19 cases from scientific literature and 16 cases from media reports. The type of stem cell and derived tissue used in these reports was diverse. Twelve cases involved adipose derived stem cells and one case involved umbilical cord blood which are both commonly used in research due to a large number of studies demonstrating safety. The remaining cases involved stem cells rarely used in research including animal based stem cells, fetal neural stem cells, olfactory mucosal stem cells, and olfactory ensheathing fetal cells.

Of the 35 reported cases, serious adverse events (SAEs) were mostly neoplastic (tumor forming), neurologic, cardiovascular, vision loss, infections, or febrile illness; 5 cases involved neoplastic complications, 4 cases involved neurologic complications, 7 involved cardiovascular complications, 3 involved vision loss (All from BioHeart Int.), 6 involved infectious complications, 2 involved febrile illness, and 2 involved autoimmune reaction. The remaining cases were not adequately described.

Of these 35 cases, only 5 cases were from the United States with three cited in scientific literature resulting in blindness after stem cells were injected into the eye. All three cases of blindness involved stem cells from BioHeart Inc which halted eye injections after FDA warning letters and ensuing court cases.

A 2019 Washington Post article reported recent adverse events (AEs) from stem cells therapy in at least 17 people after receiving umbilical cord derived stem cells between 2018 and 2019. Most of these cases were local or systemic bacterial infection. After receiving numerous reports of AEs, the CDC launched an investigation and determined the infections were probably due to contaminated stem cell products after they found bacteria in a number of unopened vials obtained from the clinics where AEs were reported.

The reports presented by Bauer et al and the Washington Post raises concern regarding the potential AEs of stem cell therapy and are important to be aware of. However, these reports only highlight relatively rare adverse events and do not reflect the safety and tolerability reported by most clinical trials.

The safety and tolerability of stem cell therapy has been clearly demonstrated in numerous studies involving large numbers of patients treated for various different conditions. While we wait for phase II/III trials the current data is encouraging and supports use of stem cell therapy in the clinical setting.

Please visit our Safety Research Archive for a list of recent clinical studies demonstrating the safety of stem cell therapy in various medical conditions

For recent news on stem cell therapy please visit New Research & News Archive