Multi-target approaches to CNS repair: olfactory mucosa-derived cells and heparan sulfates

Nat Rev Neurol. 2020 Apr;16(4):229-240. doi: 10.1038/s41582-020-0311-0. Epub 2020 Feb 25.

Abstract

Spinal cord injury (SCI) remains one of the biggest challenges in the development of neuroregenerative therapeutics. Cell transplantation is one of numerous experimental strategies that have been identified and tested for efficacy at both preclinical and clinical levels in recent years. In this Review, we briefly discuss the state of human olfactory cell transplantation as a therapy, considering both its current clinical status and its limitations. Furthermore, we introduce a mesenchymal stromal cell derived from human olfactory tissue, which has the potential to induce multifaceted reparative effects in the environment within and surrounding the lesion. We argue that no single therapy will be sufficient to treat SCI effectively and that a combination of cell-based, rehabilitation and pharmaceutical interventions is the most promising approach to aid repair. For this reason, we also introduce a novel pharmaceutical strategy based on modifying the activity of heparan sulfate, an important regulator of a wide range of biological cell functions. The multi-target approach that is exemplified by these types of strategies will probably be necessary to optimize SCI treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transplantation / methods
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Heparan Sulfate Proteoglycans / metabolism
  • Heparin / therapeutic use
  • Heparitin Sulfate / analogs & derivatives
  • Heparitin Sulfate / therapeutic use*
  • Humans
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Nerve Regeneration
  • Neuroglia
  • Olfactory Mucosa / cytology*
  • Olfactory Mucosa / physiology
  • Olfactory Receptor Neurons
  • Spinal Cord Injuries / therapy*
  • Spinal Cord Regeneration*

Substances

  • Chondroitin Sulfate Proteoglycans
  • Heparan Sulfate Proteoglycans
  • Heparin
  • Heparitin Sulfate