Endothelial and myogenic differentiation of hematopoietic progenitor cells in inflammatory myopathies

J Neuropathol Exp Neurol. 2008 Jul;67(7):711-9. doi: 10.1097/NEN.0b013e31817d8064.


Incorporation of circulating hematopoietic progenitor cells (HPCs) into damaged skeletal muscle has been proposed as a novel mechanism of tissue repair complementary to satellite cell-dependent regeneration. We studied the occurrence and myoendothelial differentiation of HPCs in muscle of patients with inflammatory myopathies. Muscle biopsies from untreated patients with dermatomyositis, polymyositis, inclusion body myositis, and controls were investigated for the expression of endothelial (CD31, von Willebrand factor, vascular endothelial growth factor receptor 2), hematopoietic (CD34, CD133, CD45), and myogenic (Pax7, MyoD) markers by immunohistochemistry and reverse-transcriptase-polymerase chain reaction. Confocal laser scanning microscopy was used to visualize coexpression of CD34, CD133, von Willebrand factor, or Pax7 on individual cells. Morphometric analysis revealed significantly increased numbers of CD133 cells per square millimeter in polymyositis and inclusion body myositis compared with controls (p < 0.001); this correlated with the density of CD45 infiltrates (p < 0.001). By confocal laser scanning microscopy, we detected several mononuclear cells that coexpressed either CD34/von Willebrand factor or CD133/Pax7 with or without CD34 reactivity, indicating endothelial or myogenic commitment of some HPCs in skeletal muscle. Rarely, CD133/CD34/Pax7 cells seemed to occupy satellite cell niches or to incorporate into preexisting myofibers. Our findings suggest that circulating HPCs colonize skeletal muscle in inflammatory conditions and provide evidence for in situ myoendothelial differentiation of some of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens / genetics
  • Antigens / metabolism
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Endothelium / drug effects
  • Endothelium / physiology*
  • Female
  • Gene Expression / physiology
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / pathology*
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology*
  • Myositis / classification
  • Myositis / pathology*
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • von Willebrand Factor / immunology


  • Antigens
  • Antigens, CD
  • PAX7 Transcription Factor
  • PAX7 protein, human
  • Von Willebrand antigen
  • von Willebrand Factor
  • Vascular Endothelial Growth Factor Receptor-2