Traumatic brain injury and stem cell treatments: A review of recent 10 years clinical trials

Traumatic brain injury (TBI) is damage to the brain by an external physical force. It may result in cognitive and physical dysfunction. It is one of the main causes of disability and death all around the world. In 2016, the worldwide incidence of acute TBI was nearly 27 million cases. Therapeutic interventions currently in use provide poor outcomes. So recent research has focused on stem cells as a potential treatment. The major objective of this study was to conduct a systematic review of the recent clinical trials in the field of stem cell transplantation for patients with TBI. The Cochrane Library, Web of Science, SCOPUS, PubMed and also Google Scholar were searched for relevant terms such as "traumatic brain injury", " brain trauma", "brain injury", "head injury", "TBI", "stem cell", and "cell transplantation" and for publications from January 2013 to June 2023. Clinical trials and case series which utilized stem cells for TBI treatment were included. The data about case selection and sample size, mechanism of injury, time between primary injury and cell transplantation, type of stem cells transplanted, route of stem cell administration, number of cells transplanted, episodes of transplantation, follow-up time, outcome measures and results, and adverse events were extracted. Finally, 11 studies met the defined criteria and were included in the review. The total sample size of all studies was 402, consisting of 249 cases of stem cell transplantation and 153 control subjects. The most commonly used cells were BMMNCs, the preferred route of transplantation was intrathecal transplantation, and all studies reported improvement in clinical, radiologic, or biochemical markers after transplantation. No serious adverse events were reported. Stem cell therapy is safe and logistically feasible and leads to neurological improvement in patients with traumatic brain injury. However, further controlled, randomized, multicenter studies with large sample sizes are needed to determine the optimal cell and dose, timing of transplantation in acute or chronic phases of TBI, and the optimal route and number of transplants.