Adipose-derived stem cells stimulate reendothelialization in stented rat abdominal aorta.
BACKGROUND
Although drug-eluting stents (DES) have been widely used for the treatment of coronary artery disease, they potentially increase the risk of late thrombosis. It is, therefore, desirable to establish a strategy to stimulate reendothelialization. Endothelial injury models have been widely used to analyze the mechanisms of coronary restenosis. However, animal models deployed with coronary stents in the blood vessels are necessary to accurately analyze the mechanisms of coronary restenosis and late thrombosis because persistent inflammation occurs around the coronary stents.


RESULTS
Coronary stents were implanted into rat abdominal aorta and adipose tissue-derived stem cells (ASC) were administered from the adventitial side. Reendothelialization was then visualized by Evans blue staining, and neointimal formation was analyzed histologically. ASC significantly stimulated reendothelialization and inhibited neointimal formation in bare metal stents (BMS)-implanted aorta. In addition, ASC promoted reendothelialization in DES-implanted aorta; however, the effects were weaker than in BMS-implanted aorta. Among the cytokines that ASC produce, adrenomedullin (AM) significantly stimulated reendothelialization and inhibited neointimal formation in BMS-implanted aorta, when an adenovirus expressing AM was administered from the adventitial side.


CONCLUSIONS
These results suggest that ASC produce several cytokines that stimulate reendothelialization and inhibit neointimal formation in stent-deployed vessels, and that AM could mediate these effects.
Department of Internal Medicine, Faculty of Medicine, University of Tokyo.
Tomohiko
T
Sato
Masao
M
Takahashi
Daishi
D
Fujita
Shigeyoshi
S
Oba
Hiroaki
H
Nishimatsu
Tetsuo
T
Nagano
Etsu
E
Suzuki
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D053607:Adrenomedullin / Q000378:metabolism; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D058426:Neointima / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D015607:Stents
D053607:Adrenomedullin