This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/1/54    most recent ATVBAHA.107.147256v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, C.-H. Articles by Stanford, W. L. Search for Related Content PubMed PubMed Citation Articles by Wang, C.-H. Articles by Stanford, W. L.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:54.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Late-Outgrowth Endothelial Cells Attenuate Intimal Hyperplasia Contributed by Mesenchymal Stem Cells After Vascular Injury

Chao-Hung Wang; Wen-Jin Cherng; Ning-I Yang; Li-Tang Kuo; Chia-Ming Hsu; Hung-I Yeh; Yii-Jenq Lan; Chi-Hsiao Yeh; William L. Stanford

From the Division of Cardiology, Department of Internal Medicine (C.-H.W., W.-J.C., N.-I.Y., L.-T.K., C.-M.H., Y.-J.L., C.-H.Y.), Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Keelung, Taiwan; the Mackay Memorial Hospital (H.-I.Y.), Mackay Medicine, Nursing and Management College, Taipei Medical University, Taiwan; and the Institute of Biomaterials and Biomedical Engineering (W.L.S.), University of Toronto, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.

Correspondence to Chao-Hung Wang, MD, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, Taiwan. E-mail bearty{at}adm.cgmh.org.tw

Abstract

Objectives— Mesenchymal stem cells (MSCs) are one of a number of cell types undergoing extensive investigation for cardiac regeneration therapy. It has not yet been determined whether this cell therapy also substantially contributes to vascular remodeling of diseased vessels.

Methods and Results— Human MSCs and a variety of progenitor and vascular cells were used for in vitro and in vivo experiments. Wire-induced vascular injury mobilized MSCs into the circulation. Compared with human aortic smooth muscle cells, MSCs exhibited a 2.8-fold increase in the adhesion capacity in vitro (P<0.001) and a 6.3-fold increase in vivo (P<0.001). In all animal models, a significant amount of MSCs contributed to intimal hyperplasia after vascular injury. MSCs were able to differentiate into cells of endothelial or smooth muscle lineage. Coculture experiments demonstrated that late-outgrowth endothelial cells (OECs) guided MSCs to differentiate toward an endothelial lineage through a paracrine effects. In vivo, cell therapy with OECs significantly attenuated the thickness of the neointima contributed by MSCs (intima/media ratio, from 3.2±0.4 to 0.4±0.1, P<0.001).

Conclusions— Tissue regeneration therapy with MSCs or cell populations containing MSCs requires a strategy to attenuate the high potential of MSCs to develop intimal hyperplasia on diseased vessels.

Mesenchymal stem cells (MSCs) are one of the cell types being used for cardiac regeneration therapy. MSCs exhibited a strong adhesive capacity and contributed to vascular remodeling of diseased vessels, such as intimal hyperplasia. Combining MSC therapy with outgrowth endothelial cells significantly modulated and attenuated this MSC-related adverse effect.

Key Words: mesenchymal stem cells • intimal hyperplasia • cell therapy • vascular remodeling