Current trends in cell therapy for pediatric acquired brain injury

Abstract

Pediatric traumatic brain injury (TBI) represents a major burden on healthcare worldwide. In the United States, TBI accounts for 435000 Emergency Department visits, 37000 hospital admissions, and approximately 2500 deaths each year. While aggressive early rehabilitation has shown some functional improvement, the acute care of TBI with focus on controlling intracranial pressure while maintaining adequate cerebral perfusion has not shown the ability to reverse neuronal injury on either a cellular or subcellular level. Preliminary investigation into the use of cell therapeutics has shown promise for the treatment of TBI in animal models. While progenitor cells may potentially act via altering the intracerebral milieu (modulation of inflammatory response and trophic factor secretion), the exact mechanism remains controversial. In addition, traditional delivery vehicles (intravenous, intra-arterial, intrathecal injections, and direct implantation) have shown significant barriers to translation coupled with inconsistent results. Therefore, investigation into novel delivery vehicles such as nanofiber scaffolds and hydrogels could enhance transplant cell viability, engraftment, and efficacy. Overall, a large amount of preclinical work remains to clearly define optimal progenitor cell type, dosage, and delivery vehicle. The optimal therapeutic benefit may be seen using a combination of therapies (controlled hypothermia, hypertonic therapy, and/or cellular therapeutics) to attack the complex pathophysiology of TBI at multiple points.