Transplantation of Human Adipose Mesenchymal Stem Cells in Non-Immunosuppressed GRMD Dogs is a Safe Procedure

Stem Cell Rev Rep. 2016 Aug;12(4):448-53. doi: 10.1007/s12015-016-9659-3.

Abstract

The possibility to treat Duchenne muscular dystrophy (DMD), a lethal X-linked disorder, through cell therapy with mesenchymal stromal cells (MSCs) has been widely investigated in different animal models. However, some crucial questions need to be addressed before starting human therapeutic trials, particularly regarding its use for genetic disorders. How safe is the procedure? Are there any side effects following mesenchymal stem cell transplantation? To address these questions for DMD the best model is the golden retriever muscular dystrophy dog (GRMD), which is the closest model to the human condition displaying a much longer lifespan than other models. Here we report the follow-up of 5 GRMD dogs, which were repeatedly transplanted with human adipose-derived mesenchymal stromal cells (hASC), derived from different donors. Xenogeneic cell transplantation, which was done without immunosuppression, was well tolerated in all animals with no apparent long-term adverse effect. In the present study, we show that repeated heterologous stem-cell injection is a safe procedure, which is fundamental before starting human clinical trials.

Keywords: Cell therapy; GRMD dogs; Human multipotent mesenchymal stromal cells; Muscular dystrophy; Xenotransplantation.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Cells, Cultured
  • Creatine Kinase / blood
  • Disease Models, Animal
  • Dog Diseases / blood
  • Dog Diseases / therapy*
  • Dogs
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Immunocompetence
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology*
  • Muscular Dystrophy, Animal / blood
  • Muscular Dystrophy, Animal / therapy*
  • Muscular Dystrophy, Duchenne / blood
  • Muscular Dystrophy, Duchenne / therapy
  • Reproducibility of Results
  • Time Factors
  • Transplantation, Heterologous
  • Treatment Outcome

Substances

  • Creatine Kinase