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

Nature Medicine volume 8, pages 403–409 (2002)Cite this article

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.

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Figure 1: Contribution of bone-marrow cells to healing and lesion formation after mechanical injury.
Figure 2: Detection of bone marrow–derived smooth-muscle cells in transplant-associated arteriosclerosis.
Figure 3: Bone marrow–derived smooth-muscle cells detected in atherosclerotic plaques.
Figure 4: Differentiation of hematopoietic stem cells into smooth-muscle cells.

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Acknowledgements

We thank H. Kato, T. Hasegawa, Y. Sugawara, M. Kinoshita and N. Nangi for technical assistance. This study was supported in part by grants from the Japan Heart Foundation, the Japan Foundation of Cardiovascular Research, the Naito Foundation, the Yamanouchi Foundation for Research on Metabolic Disorders, the Japan Research Foundation for Clinical Pharmacology, the NOVARTIS Foundation for the Promotion of Science, the Shionogi Foundation, the Asahi Glass Foundation, the Kanae foundation, the Takeda Medical Research Foundation, the Mitsukoshi health and welfare foundation and the Terumo Life Science Foundation (to S.M.).

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Authors and Affiliations

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

    Masataka Sata, Yasunobu Hirata & Ryozo Nagai

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

    Akio Saiura & Masatoshi Makuuchi

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

    Atsushi Kunisato & Hisamaru Hirai

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

    Akihiro Tojo

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

    Seiji Okada & Takeshi Tokuhisa

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

    Masataka Sata

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  1. Masataka Sata
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Correspondence to Masataka Sata.

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Sata, M., Saiura, A., Kunisato, A. et al. Hematopoietic stem cells differentiate into vascular cells that participate in the pathogenesis of atherosclerosis. Nat Med 8, 403–409 (2002). https://doi.org/10.1038/nm0402-403

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