Late-outgrowth endothelial cells attenuate intimal hyperplasia contributed by mesenchymal stem cells after vascular injury.
OBJECTIVE
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.


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.
Wang
Chao-Hung
CH
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, Taiwan. bearty@adm.cgmh.org.tw
Cherng
Wen-Jin
WJ
Yang
Ning-I
NI
Kuo
Li-Tang
LT
Hsu
Chia-Ming
CM
Yeh
Hung-I
HI
Lan
Yii-Jenq
YJ
Yeh
Chi-Hsiao
CH
Stanford
William L
WL
D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D023903:Coronary Restenosis / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000502:physiology*; D005263:Femoral Artery / Q000293:injuries / Q000503:physiopathology*; D006801:Humans; D006965:Hyperplasia; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D017539:Tunica Intima / Q000166:cytology / Q000473:pathology* / Q000503:physiopathology