Feasibility study of canine epidermal neural crest stem cell transplantation in the spinal cords of dogs

Barbara G. McMahill, Mathieu Spriet, Sílvia Sisó, Michael D. Manzer, Gaela Mitchell, Jeannine McGee, Tanya C. Garcia, Dori L Borjesson, Maya Sieber-Blum, Jan Nolta, Beverly Sturges

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

This pilot feasibility study aimed to determine the outcome of canine epidermal neural crest stem cell (cEPI-NCSC) grafts in the normal spinal cords of healthy bred-for-research dogs. This included developing novel protocols for (a) the ex vivo expansion of cEPI-NCSCs, (b) the delivery of cEPI-NCSCs into the spinal cord, and (c) the labeling of the cells and subsequent tracing of the graft in the live animal by magnetic resonance imaging. A total of four million cEPI-NCSCs were injected into the spinal cord divided in two locations. Differences in locomotion at baseline and post-treatment were evaluated by gait analysis and compared with neurological outcome and behavioral exams. Histopathological analyses of the spinal cords and cEPI-NCSC grafts were performed at 3 weeks post-transplantation. Neurological and gait parameters were minimally affected by the stem cell injection. cEPI-NCSCs survived in the canine spinal cord for the entire period of investigation and did not migrate or proliferate. Subsets of cEPI-NCSCs expressed the neural crest stem cell marker Sox10. There was no detectable expression of markers for glial cells or neurons. The tissue reaction to the cell graft was predominantly vascular in addition to a degree of reactive astrogliosis and microglial activation. In the present study, we demonstrated that cEPI-NCSC grafts survive in the spinal cords of healthy dogs without major adverse effects. They persist locally in the normal spinal cord, may promote angiogenesis and tissue remodeling, and elicit a tissue response that may be beneficial in patients with spinal cord injury.

Original languageEnglish (US)
Pages (from-to)1173-1186
Number of pages14
JournalStem cells translational medicine
Volume4
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • Adult stemcells
  • Canine epidermal neural crest stem cell
  • Canine epidermal neural crest stem cells
  • Dog model
  • Epidermal neural crest stem cell
  • Spinal cord injury

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology

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    McMahill, B. G., Spriet, M., Sisó, S., Manzer, M. D., Mitchell, G., McGee, J., Garcia, T. C., Borjesson, D. L., Sieber-Blum, M., Nolta, J., & Sturges, B. (2015). Feasibility study of canine epidermal neural crest stem cell transplantation in the spinal cords of dogs. Stem cells translational medicine, 4(10), 1173-1186. https://doi.org/10.5966/sctm.2015-0018