Generation of Equine-Induced Pluripotent Stem Cells and Analysis of Their Therapeutic Potential for Muscle Injuries

Cell Transplant. 2016 Nov;25(11):2003-2016. doi: 10.3727/096368916X691691.

Abstract

Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/ mdx mice. The histopathology results showed that E-iPSC-transplanted mice exhibited enhanced muscle regeneration compared to controls. In addition, E-iPSC-derived myofibers were observed in the injured muscles. In conclusion, we show that E-iPSCs could be successfully generated from equine ADSCs and transplanted into injured muscles and that E-iPSCs have the capacity to induce regeneration of injured muscles.

Keywords: Horse; Induced pluripotent stem cells (iPSCs); Muscle regeneration; Transplantation.

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Cellular Reprogramming
  • Elapid Venoms / pharmacology
  • Embryoid Bodies / metabolism
  • Embryoid Bodies / pathology
  • Gene Expression / drug effects
  • Horses
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / transplantation*
  • Kruppel-Like Factor 4
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mice, Transgenic
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiology*
  • Muscular Dystrophies / pathology
  • Muscular Dystrophies / therapy*
  • Myogenin / genetics
  • Myogenin / metabolism
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Regeneration
  • Stem Cells / cytology
  • Stem Cells / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Elapid Venoms
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Myogenin
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • Transcription Factors
  • notexin