Safety of neural stem cell therapy for traumatic brain injury

Firearm injury is a serious public health problem in the United States (US) costing more than $70-75 billion annually [1,2]. Despite increasing incidence, timely neurosurgical intervention aided with improved neuroimaging and advances in acute trauma management have lowered the firearm fatality rate {Joseph, 2014 #42;Lin, 2012 #164;Young, 2008 #56}. Thus, among the estimated 5.3 million people living in the US with traumatic brain injury (TBI)-related disability, the proportion of gun-shot wound survivors has been rising steadily [3-8]. Among head injuries, penetrating injuries (PTBI) are associated with the worst outcomes [9,10], and no effective restorative treatment beyond physical therapy is currently available to mitigate post-TBI disability [9-11]. There is an urgent need to explore additional treatment options to address long-term TBI related disabilities. Since the demonstration of ability to culture, expand human fetal neural stem in vitro, their genetic modification and engraftment in rodents post transplantation [12-15] multiple insights into how embryonic transplant derived neurons integrate into adult circuits (Gotz 2016) and technical advances studies have supported clinically relevant studies in immunocompromised or immunosuppressed animal [16,17]. Athymic rats with TBI (Haus 2016), or Parkinson disease (Snyder 2016) have been used with neural stem cells derived from induced human pluripotent stem cells to demonstrate the viability of the approach.