Traumatic Brian Injuries (TBI) are a leading cause of death & disability worldwide. 1.7 million American’s experience a TBI leading to hospitalization/year; this projects to 230,000 Californians. TBI often results in permanent cognitive and emotional deficits; the cost of TBI far exceeds the cost of injury to any other body part. There are no effective treatments for TBI, making TBI one of the most unmet medical needs based on both the number of those affected and cost to society. 

In our QUEST grant (DISC2-10195), we tested 2 embryonic and 2 fetal stem cell lines in a rodent model of TBI. Of these, human neural stem cells (hNSCs) generated from the embryonic stem cell line, Shef6, proved to be efficacious on multiple outcome measures. Shef6 hNSCs reduced anxiety and improved learning and memory in rats with moderate to severe TBI. These positive effects were observed after transplants either 9 days or 30 days after injury. We also discovered several possible mechanisms of action, including making new neurons and glia (support cells), helping the injured brain to make its own new neurons, protecting the brain from ongoing degeneration, and reducing the long-term inflammation commonly associated with TBI.

In the future, we will work with an industry partner (AIVITA) to produce larger quantities of Shef6 human neural stem cells (hNSCs), sorting them to enrich for the neural stem cell marker CD133, and freezing them using industry recognized methods of scale up and manufacturing controls (CMC). These frozen vials of Shef6 hNSCs will be delivered to two sites to repeat safety and long-term efficacy testing in rodents and none-human primates. 

Our team combines the neurotrauma expertise of Cummings & Anderson (UC, Irvine), with Nistor (CMC process development, AIVITA), Loring (analysis of genomic data, Aspen Neuro), Groysman & Chen (stem cell trials for stroke & TBI @ UC Irvine), and Macel Daadi (Southwest National Primate Research Center).