Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

Yee Shuan Lee, Lucy Funk, Jae Lee, Mary B Bunge

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury (SCI) and is currently in clinical trials. In our continuing efforts to improve Schwann cell transplantation strategies, we sought to determine the combined effects of Schwann cell transplantation with macrophage depletion. Since macrophages are major inflammatory contributors to the acute spinal cord injury, and are the major phagocytic cells, we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after SCI. To test this hypothesis, rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or not. In rat subjected to macrophage depletion, liposomes filled with clodronate were intraperitoneally injected at 1, 3, 6, 11, and 18 days post injury. Rats not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered saline. Schwann cells were transplanted 1 week post injury in all rats. Biotinylated dextran amine (BDA) was injected at thoracic level 5 to evalute axon regeneration. The Basso, Beattie, and Bresnahan locomotor test, Gridwalk test, and sensory test using von Frey filaments were performed to assess functional recovery. Immunohistochemistry was used to detect glial fibrillary acidic protein, neurofilament, and green fluorescent protein (GFP), and also to visulize BDA-labelled axons. The GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained slides. The numbers of BDA-positive axons were also quantified. At 8 weeks after Schwann cell transplantation, there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation alone.

Original languageEnglish (US)
Pages (from-to)684-691
Number of pages8
JournalNeural Regeneration Research
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2018

Keywords

  • axon regeneration
  • cell transplantation
  • clodronate
  • clodrosome
  • cyst
  • glial scar
  • liposome
  • neuroprotection
  • Schwann cell
  • Schwann cell survival

ASJC Scopus subject areas

  • Developmental Neuroscience

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