Adverse events of cell therapy clinical trials in human chronic spinal cord injury, a systematic review and meta-analysis.

ABSTRACT

Spinal cord injury is a lesion with high mortality and significant morbidities. After the primary injury, during six months, a cascade of secondary cellular and molecular events makes the lesion chronic. Recently, cell-based clinical trials as a new procedure have been gradually tested to improve the symptoms of patients. Each treatment method is associated with different adverse events. Based on the PRISMA flow diagram of the identified records, and after multistep screening, finally in 76 reviewed studies with 1633 cases and 189 controls, 64 types of adverse events in 12 categories were recorded in 45 studies. The most common adverse events were transient backache and meningism (90%) and cord malacia (80%). The cell therapy method in which the treatment was associated with more adverse events was Olfactory ensheathing cell and bone marrow mesenchymal stem cell combination therapy in 55%, and the adverse events were less with the embryonic stem cell in 2.33% of patients. In a meta-analysis, the total prevalence of adverse events in cell therapy was 19% and the highest pulled effect size belonged to urinary tract and localized adverse events. Also, the total prevalence of adverse events in 14 cell therapy methods was 18% and four cell types (neural stem cell, bone marrow hematopoietic stem cell, embryonic stem cell, and umbilical cord mesenchymal stem cell) had the most effect. None of the adverse events were reported on the 4 (life-threatening consequences) and 5 (death) grading scales. We concluded that the frequency of life-threatening adverse events following cell therapy clinical trials in chronic spinal cord injury patients is very scarce and can be ignored.