Treatment of perianal fistulas with human embryonic stem cell-derived mesenchymal stem cells: a canine model of human fistulizing Crohn's disease

Regen Med. 2016 Jan;11(1):33-43. doi: 10.2217/rme.15.69. Epub 2015 Sep 21.

Abstract

Aim: To evaluate the safety and efficacy of intralesional injection of human embryonic stem cell (hESC)-derived mesenchymal stem/stromal cells (MSCs) in canine anal furunculosis dogs.

Materials & methods: Dogs naturally develop an immune-mediated disease called canine anal furunculosis, which shares many features with human fistulizing Crohn's disease.

Results: The hESC-MSCs were well tolerated and 1 month postinjection, accompanied by reduced serum levels of IL-2 and IL-6, two inflammatory cytokines associated with Crohn's disease. All six dogs were found to be completely free of fistulas at 3 months postinjection. However, at 6 months, two dogs had some fistula relapse.

Conclusion: Results of this study provide the first evidence of the safety and therapeutic potential of hESC-MSCs in a large animal model.

Keywords: Crohn's disease; canine perianal furunculosis; human embryonic stem cells; mesenchymal stem cells; perianal fistulas; pluripotent stem cells.

MeSH terms

  • Animals
  • Crohn Disease / drug therapy
  • Crohn Disease / therapy*
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use
  • Cytokines / blood
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Follow-Up Studies
  • Heterografts
  • Human Embryonic Stem Cells / cytology*
  • Humans
  • Immunomodulation
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Rectal Fistula / therapy*
  • Stromal Cells / cytology

Substances

  • Cytokines
  • Cyclosporine