Clinical Lessons of MSC Therapy Over the Past 15 Years: A Systematic Review and Meta-Analysis

Abstract Background: Despite increasing clinical investigations in emphasizing the safety of MSC therapy in different populations with different diseases, recently, no article overall reviewed the side 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 MSC.Methods: The databases of PubMed, Embase, Web of Science and Scopus were searched from onset until March 1st, 2021. Results: All side events were displayed as odds ratio (OR) and 95% CI (confidential intervals). Totally, 62 randomized clinical trials (RCTs) that enrolled 3546 participants diagnosed with various diseases (about 20 kinds of diseases) treated with intravenous or local implantation vs placebo, or no treatment were included. All studies were high quality, neither serious publication bias nor serious adverse events (such as death and infection) were discovered across included studies. The pooled analysis demonstrated that MSC administration was extremely associated with transient fever [OR, 3.65, 95% CI: 2.05 to 6.49, p<0.01], administration site conditions [OR, 1.98, 95% CI: 1.01 to 3.87, p=0.05], constipation [OR, 2.45, 95% CI: 1.01 to 5.97, p=0.05], fatigue [OR, 2.99, 95% CI: 1.06 to 8.44, p=0.04], and sleeplessness [OR, 5.90, 95% CI: 1.04 to 33.47, p=0.05]. Interestingly, MSC administration trended to lower rather than boost the incidence rate of arrhythmia [OR, 0.62, 95% CI: 0.36 to 1.07, p=0.09]. Conclusions: Conclusively, MSC administration was safe in different populations compared with the other placebo modalities.