Researchers from the University of California San Diego School of Medicine (CA, USA) have discovered that a molecule associated with myelin could stimulate axonal growth in neural precursor cells (NPCs) and induced pluripotent (iPSC)-derived neural stem cells – a finding that could aid research into developing methods for repairing and regrowing neurons in the treatment of spinal cord injuries.
Myelin is well-known for preventing the growth of new neural cells, therefore inhibiting the repair of damaged nerves after spinal cord injury.
In this study, published online in Science Translational Medicine, researchers monitored neurite outgrowth on a myelin substrate from NPCs and neural stem cells. They reported a neurite outgrowth three-times that of cells grown without the myelin substrate. Consequent studies involving rats with spinal cord injuries revealed that rat NPCs and human pluripotent-derived neural stem cells implanted at the site of injury were strongly associated with rat myelin. Both neuron types stimulated more axon growth in the CNS white matter than in grey matter.
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Mark Tuszynski, the director of the University of California San Diego Translational Neuroscience Institute, explained: “It’s a really remarkable finding because myelin is known to be a potent inhibitor of adult axon regeneration, but that isn’t the case with precursor neurons, or those derived from stem cells.”
Tuszynski and colleagues identified Negr1 as the potential mediator of the neurite outgrowth. Negr1 encourages growth during embryonic development, before myelin begins its inhibitory effect.
The use of NPCs in spinal cord injuries might be the next step in successfully repairing and regrowing damaged neurons. Neural stem cells “extend tens of thousands of axons out of the injury site for distances of up to 50 mm,” commented Tuszynski.
“Adult axons, on the other hand, when coaxed to grow, extend 100 axons for a distance of 1 mm. These findings identify why axon outgrowth from neural stem cell implants is so much better than injured adult axons.”
The report supports the modern approach of using stem cells to repair spinal cord injuries. It is the first to identify Negr1 and its pivotal role in embryonic neural development. The relationship between myelin molecules and neural stem cells needs to be better explored, however, Tuszynski concluded that it: “could potentially be exploited for neural repair after spinal cord injury.”
Sources: Poplawski GHD, Lie R, Hunt M et al. Adult rat myelin enhances axonal outgrowth from neural stem cells. Sci. Transl. Med. doi:10.1126/scitranslmed.aal2563 (2018) (Epub ahead of print); www.eurekalert.org/pub_releases/2018-05/uoc–iab052318.php