The safety of MSC therapy over the past 15 years: a meta-analysis.

Background: Despite increasing clinical investigations emphasizing the safety of mesenchymal stem cell (MSC) therapy in different populations with different diseases, no article has recently reviewed the adverse events in all populations.

Aim: To evaluate the safety of MSC therapy in all populations receiving MSC therapy and explore the potential heterogeneities influencing the clinical application of MSCs.

Methods: The PubMed, Embase, Web of Science and Scopus databases were searched from onset until 1 March 2021.

Results: All adverse events are displayed as odds ratios (ORs) and 95% CIs (confidential intervals). In total, 62 randomized clinical trials were included that enrolled 3546 participants diagnosed with various diseases (approximately 20 types of diseases) treated with intravenous or local implantation versus placebo or no treatment. All studies were of high quality, and neither serious publication bias nor serious adverse events (such as death and infection) were discovered across the included studies. The pooled analysis demonstrated that MSC administration was closely associated with transient fever (OR, 3.65, 95% CI 2.05-6.49, p < 0.01), administration site adverse events (OR, 1.98, 95% CI 1.01-3.87, p = 0.05), constipation (OR, 2.45, 95% CI 1.01-5.97, p = 0.05), fatigue (OR, 2.99, 95% CI 1.06-8.44, p = 0.04) and sleeplessness (OR, 5.90, 95% CI 1.04-33.47, p = 0.05). Interestingly, MSC administration trended towards lowering rather than boosting the incidence rate of arrhythmia (OR, 0.62, 95% CI 0.36-1.07, p = 0.09).

Conclusions: Conclusively, MSC administration was safe in different populations compared with other placebo modalities.