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Article
Nature Medicine  8, 403 - 409 (2002)
doi:10.1038/nm0402-403

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

Masataka Sata1, 6, Akio Saiura2, Atsushi Kunisato3, Akihiro Tojo4, Seiji Okada5, Takeshi Tokuhisa5, Hisamaru Hirai3, Masatoshi Makuuchi2, Yasunobu Hirata1 & Ryozo Nagai1

1  Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan

2  Department of Surgery, University of Tokyo Graduate School of Medicine, Tokyo, Japan

3  Department of Hematology and Oncology, University of Tokyo Graduate School of Medicine, Tokyo, Japan

4  Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan

5  Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba, Japan

6  Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Kawaguchi, Saitama, Japan

Correspondence should be addressed to Masataka Sata sata-2im@h.u-tokyo.ac.jp
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.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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