Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells

Homma, Koichiro; Sone, Masakatsu; Taura, Daisuke; Yamahara, Kenichi; Suzuki, Yutaka; Takahashi, Kazutoshi; Sonoyama, Takuhiro; Inuzuka, Megumi; Fukunaga, Yasutomo; Tamura, Naohisa; Itoh, Hiroshi; Yamanaka, Shinya; Nakao, Kazuwa

doi:10.1016/j.atherosclerosis.2010.04.021

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Volume 212, Issue 1 , Pages 42-47, September 2010

Sirt1 plays an important role in mediating greater functionality of human ES/iPS-derived vascular endothelial cells

Koichiro Homma
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
- Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
Masakatsu Sone
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
- Corresponding author. . Tel.: +81 75 751 3170; fax: +81 75 771 9452.
Daisuke Taura
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Kenichi Yamahara
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Yutaka Suzuki
- Stem Cell and Drug Discovery Institute, Kyoto, Japan
Kazutoshi Takahashi
- Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
- Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto, Japan
Takuhiro Sonoyama
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Megumi Inuzuka
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Yasutomo Fukunaga
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Naohisa Tamura
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
Hiroshi Itoh
- Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
Shinya Yamanaka
- Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
- Center for iPS Cell Research and Application (CiRA), Institute for Integrated Cell-Material Sciences, Kyoto, Japan
Kazuwa Nakao
- Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan

Received 14 December 2009; received in revised form 18 March 2010; accepted 14 April 2010. published online 20 May 2010.

Abstract

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).

Methods and 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.

Keywords: Stem cells, Endothelium, Sirt1