Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells.
OBJECTIVE
We previously succeeded in inducing and isolating vascular endothelial cells (ECs) from both human embryonic stem (ES) and induced pluripotent stem (iPS) cells. Here, we compared the functionality of human adult ECs (HAECs), human ES-derived ECs (ESECs) and human iPS-derived ECs (iPSECs).


RESULTS
We compared the cell proliferative potential, potential for migration, and tolerance to oxidative stress. ESECs were significantly superior to HAECs in all of these cell functions. The cell functions of iPSECs were comparable to those of ESECSs and also superior to HAECs. We then analyzed the gene expressions of HAECs, ESECs and iPSECs, and observed that the expression level of Sirt1, a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase, is higher in ESECs and iPSECs than in HAECs. The inhibition of Sirt1 with a Sirt1-specific inhibitor and siRNA antagonized these differences between the three types of cells.


CONCLUSIONS
Sirt1 plays a key role in the high cellular function of ESECs and iPSECs. Although further in vivo investigations are required, this study initially demonstrated the potential of ESECs and iPSECs as the cell source for regenerative medicine, and also showed the potential of ES cells as a useful tool for elucidating the molecular mechanism of cell aging.
Homma
Koichiro
K
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Sone
Masakatsu
M
Taura
Daisuke
D
Yamahara
Kenichi
K
Suzuki
Yutaka
Y
Takahashi
Kazutoshi
K
Sonoyama
Takuhiro
T
Inuzuka
Megumi
M
Fukunaga
Yasutomo
Y
Tamura
Naohisa
N
Itoh
Hiroshi
H
Yamanaka
Shinya
S
Nakao
Kazuwa
K
D000328:Adult; D001011:Aorta / Q000166:cytology / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000201:enzymology*; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000201:enzymology*; D018919:Neovascularization, Physiologic; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D056572:Histone Deacetylase Inhibitors; D016877:Oxidants; D012333:RNA, Messenger; C447939:SIRT1 protein, human; D056564:Sirtuin 1