title: Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan. sata-2im@h.u-tokyo.ac.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Akio
authors.initials: A
authors.lastname: Saiura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kunisato
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tojo
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Hisamaru
authors.initials: H
authors.lastname: Hirai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology*; D002454:Cell Differentiation; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology; D049452:Green Fluorescent Proteins; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D066298:In Vitro Techniques; D007763:Lac Operon; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D051381:Rats
chemical_list: D001057:Apolipoproteins E; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins