Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury

Neural stem cells (NSCs) expressing GFP were embedded into fibrin matrices containing growth factor cocktails and grafted to sites of severe spinal cord injury. Grafted cells differentiated into multiple cellular phenotypes, including neurons, which extended large numbers of axons over remarkable distances. Extending axons formed abundant synapses with host cells. Axonal growth was partially dependent on mammalian target of rapamycin (mTOR), but not Nogo signaling. Grafted neurons supported formation of electrophysiological relays across sites of complete spinal transection, resulting in functional recovery. Two human stem cell lines (566RSC and HUES7) embedded in growth-factor-containing fibrin exhibited similar growth, and 566RSC cells supported functional recovery. Thus, properties intrinsic to early-stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth, resulting in formation of new relay circuits that significantly improve function. These therapeutic properties extend across stem cell sources and species. [Display omitted] ► Neural stem cells grow axons over very long distances after severe spinal cord injury ► New synaptic relays are formed, improving electrophysiological and functional outcome ► Rodent and human neural stem cells exhibit similar growth properties ► Mechanisms intrinsic to early-stage neurons overcome adult nervous system inhibition Following severe spinal cord injury in rats, functional outcomes can be improved by the engraftment of neural stem cells embedded in a matrix that contains a growth factor cocktail. The resulting neurons extend axons over long distances and form reciprocal synaptic connections with neurons from the host.