Human adult olfactory neural progenitors rescue axotomized rodent rubrospinal neurons and promote functional recovery

Ming Xiao, Kathleen M. Klueber, Chengliang Lu, Zhanfang Guo, Charles T. Marshall, Heming Wang, Fred J. Roisen

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Previously, our lab reported the isolation of patient-specific neurosphere-forming progenitor lines from human adult olfactory epithelium from cadavers as well as patients undergoing nasal sinus surgery. RT-PCR and ELISA demonstrated that the neurosphere-forming cells (NSFCs) produced BDNF. Since rubrospinal tract (RST) neurons have been shown to respond to exogenous BNDF, it was hypothesized that if the NSFCs remained viable following engraftment into traumatized spinal cord, they would rescue axotomized RS neurons from retrograde cell atrophy and promote functional recovery. One week after a partial cervical hemisection, GFP-labeled NSFCs suspended in Matrigel® matrix or Matrigel® matrix alone was injected into the lesion site. GFP-labeled cells survived up to 12 weeks in the lesion cavity or migrated within the ipsilateral white matter; the apparent number and mean somal area of fluorogold (FG)-labeled axotomized RST neurons were greater in the NSFC-engrafted rats than in lesion controls. Twelve weeks after engraftment, retrograde tracing with FG revealed that some RST neurons regenerated axons 4-5 segments caudal to the engraftment site; anterograde tracing with biotinylated dextran amine confirmed regeneration of RST axons through the transplants within the white matter for 3-6 segments caudal to the grafts. A few RST axons terminated in gray matter close to motoneurons. Matrix alone did not elicit regeneration. Behavioral analysis revealed that NSFC-engrafted rats displayed better performance during spontaneous vertical exploration and horizontal rope walking than lesion Matrigel® only controls 11 weeks post transplantation. These results emphasize the unique potential of human olfactory neuroepithelial-derived progenitors as an autologous source of stem cells for spinal cord repair.

Original languageEnglish
Pages (from-to)12-30
Number of pages19
JournalExperimental Neurology
Volume194
Issue number1
DOIs
StatePublished - Jul 2005

Bibliographical note

Funding Information:
We thank Dr. S.R. Whittemore for assistance with the GFP transfection; Dr. S.M. Onifier for help in planning the behavioral studies and for reading the manuscript; Mrs. C. Ekstrom for help in preparing the manuscript; Dr. W. Tetzlaff for helpful comments and advice. This work was supported by a grant from NIH #992558.

Keywords

  • Axonal regeneration
  • BDNF
  • Functional recovery
  • Olfactory progenitors
  • Red nucleus
  • Spinal cord injury

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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