Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis

Nat Med. 2002 Apr;8(4):403-9. doi: 10.1038/nm0402-403.


Excessive accumulation of smooth-muscle cells (SMCs) has a key role in the pathogenesis of vascular diseases. It has been assumed that SMCs derived from the outer medial layer migrate, proliferate and synthesize extracellular matrix components on the luminal side of the vessel. Although much effort has been devoted to targeting migration and proliferation of medial SMCs, there is no effective therapy that prevents occlusive vascular remodeling. We show here that in models of post-angioplasty restenosis, graft vasculopathy and hyperlipidemia-induced atherosclerosis, bone-marrow cells give rise to most of the SMCs that contribute to arterial remodeling. Notably, purified hematopoietic stem cells differentiate into SMCs in vitro and in vivo. Our findings indicate that somatic stem cells contribute to pathological remodeling of remote organs, and may provide the basis for the development of new therapeutic strategies for vascular diseases through targeting mobilization, homing, differentiation and proliferation of bone marrow-derived vascular progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Arteriosclerosis / etiology*
  • Arteriosclerosis / pathology*
  • Cell Differentiation
  • Cell Division
  • Cell Movement
  • Cells, Cultured
  • Disease Models, Animal
  • Graft Occlusion, Vascular / etiology
  • Graft Occlusion, Vascular / pathology
  • Green Fluorescent Proteins
  • Hematopoietic Stem Cells / pathology*
  • In Vitro Techniques
  • Lac Operon
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Muscle, Smooth, Vascular / pathology*
  • Rats


  • Apolipoproteins E
  • Luminescent Proteins
  • Green Fluorescent Proteins