Human neural stem cell (hNSC) derived exosomes vs CSC14 hNSCs for the treatment of traumatic brain injury (TBI)

We have show that human neural stem cells (hNSC) derived for Shef6 embryonic stem cells have efficacy in a rat model of penetrating head injury - a moderate to severe traumatic brain injury (TBI). One problem with any stem cell based treatment is that the live cellular product will trigger inflammation and rejection by the recipient's immune system - necessitating long-term immunosuppression for the patient. Our prior CIRM funded work suggested that one mechanism of action of hNSCs was via sub-cellular products released by the hNSCs and that one might not need the hNSCs to engraft and survive long-term in the host. To test the hypothesis that extracellular vesicles (EVs) from the hNSC are capable of reducing inflammation and the cognitive deficits associated with brain injuries, we tested Shef6 hNSC derived EVs in a mouse model of repeat mild concussions. While we did observe a reduction in the overall extent of brain injury via H&E staining, we did not observe an improvement in cognitive function nor in the overall level of inflammation as measured by IBA1 positive microglia.

We have shown that human neural stem cells (hNSC) derived from Shef6 embryonic stem cells have efficacy in a rat model of penetrating head injury - a moderate to severe traumatic brain injury (TBI). One problem with any stem cell based treatment is that the live cellular product will trigger inflammation and rejection by the recipient's immune system - necessitating long-term immunosuppression for the patient. Our prior CIRM-funded work suggested that one mechanism of action of hNSCs was via sub-cellular products released by the hNSCs and that one might not need the hNSCs to engraft and survive long-term in the host. To test the hypothesis that extracellular vesicles (EVs) from the hNSC can reduce inflammation and the cognitive deficits associated with brain injuries, we tested Shef6 hNSC-derived EVs in a mouse model of repeat mild concussions. While we did observe a reduction in the overall extent of brain injury via H&E staining, we did not observe an improvement in cognitive function nor the overall level of inflammation as measured by IBA1 positive microglia.