Operation spinal cord regeneration: Patterning information residing in extracellular matrix glycosaminoglycans
Alexander Lu, 1 , 2 Alaina Baker‐Nigh, PhD, 1 , 2 and Peng Sun, MD, PhD 3


Introduction
Spinal cord injuries are devastating, with many complications beyond paralysis and loss of sensory function. Although spinal cord regeneration can revolutionize treatment for spinal cord injuries, the goal has not yet been achieved. The regenerative mechanism of axolotls demonstrates that the regeneration is a repeat of developmental process that all animals have all the genes, but axolotls have both the genes and the patterning information to do it at the adult stage.
Methods
A narrative review was conducted. Relevant studies were collected via an English‐language PubMed database search and those known to the authors.
Results
Research during the past 30 years reveals that growth factors, along with spinal cord extracellular matrix, especially glycosaminoglycans, regulates axonal regrowth. Degrading chondroitin sulfate glycosaminoglycans by injecting the bacterial enzyme chondroitinase improves axonal sprouting and functional recovery after spinal cord injury in both rodents and rhesus monkeys. Furthermore, the brain is one of the first organs to develop during the embryonic period, and heparan sulfate glycosaminoglycans are key molecules required for brain development.
Conclusions
Patterning information residing in glycosaminoglycans might be key elements in restricting spinal cord regeneration. A recommended solution is not to edit the human genome, considering the conserved signaling pathways between animals, but to take advantage of the regenerative mechanism of axolotls and the current knowledge about the pattern‐forming glycosaminoglycans for successful spinal cord regeneration and clinical applications.