Functional skeletal muscle regeneration from differentiating embryonic stem cells

Nat Med. 2008 Feb;14(2):134-43. doi: 10.1038/nm1705. Epub 2008 Jan 20.


Little progress has been made toward the use of embryonic stem (ES) cells to study and isolate skeletal muscle progenitors. This is due to the paucity of paraxial mesoderm formation during embryoid body (EB) in vitro differentiation and to the lack of reliable identification and isolation criteria for skeletal muscle precursors. Here we show that expression of the transcription factor Pax3 during embryoid body differentiation enhances both paraxial mesoderm formation and the myogenic potential of the cells within this population. Transplantation of Pax3-induced cells results in teratomas, however, indicating the presence of residual undifferentiated cells. By sorting for the PDGF-alpha receptor, a marker of paraxial mesoderm, and for the absence of Flk-1, a marker of lateral plate mesoderm, we derive a cell population from differentiating ES cell cultures that has substantial muscle regeneration potential. Intramuscular and systemic transplantation of these cells into dystrophic mice results in extensive engraftment of adult myofibers with enhanced contractile function without the formation of teratomas. These data demonstrate the therapeutic potential of ES cells in muscular dystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiotoxins
  • Cell Differentiation*
  • Cell Transplantation
  • DNA-Binding Proteins / metabolism
  • Dystrophin / metabolism
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / transplantation
  • Mesoderm / embryology
  • Mice
  • Mice, Inbred mdx
  • Muscle Contraction
  • Muscle Development
  • Muscle, Skeletal / physiology*
  • Muscular Dystrophy, Animal
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / isolation & purification
  • Paired Box Transcription Factors / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Regeneration*
  • Teratoma / pathology
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Cardiotoxins
  • DNA-Binding Proteins
  • Dystrophin
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Rag2 protein, mouse
  • Pax3 protein, mouse
  • Receptor, Platelet-Derived Growth Factor alpha
  • Vascular Endothelial Growth Factor Receptor-2