Endothelial and myogenic differentiation of hematopoietic progenitor cells in inflammatory myopathies.
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.
Hollemann
David
D
Department of Blood Group Serology and Transfusion Medicine, Institute of Neurology, Medical University Vienna, Austria.
Budka
Herbert
H
Löscher
Wolfgang N
WN
Yanagida
Genya
G
Fischer
Michael B
MB
Wanschitz
Julia V
JV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004727:Endothelium / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology*; D009220:Myositis / Q000145:classification / Q000473:pathology*; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014841:von Willebrand Factor / Q000276:immunology
D000941:Antigens; D015703:Antigens, CD; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D040301:Vascular Endothelial Growth Factor Receptor-2