Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling

Kento Tateishi; Eishi Ashihara; Shoken Honsho; Naofumi Takehara; Tetsuya Nomura; Tomosaburo Takahashi; Tomomi Ueyama; Masaaki Yamagishi; Hitoshi Yaku; Hiroaki Matsubara; Hidemasa Oh

doi:10.1016/j.bbrc.2006.11.096

Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling

Kento Tateishi, Eishi Ashihara, Shoken Honsho, Naofumi Takehara, Tetsuya Nomura, Tomosaburo Takahashi, Tomomi Ueyama, Masaaki Yamagishi, Hitoshi Yaku, Hiroaki Matsubara, Hidemasa Oh

Research output: Contribution to journal › Article › peer-review

71 Citations (Scopus)

Abstract

Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardiomyocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3β may be crucial modulators for hCSC maintenance in human heart.

Original language	English
Pages (from-to)	635-641
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	352
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2006.11.096
Publication status	Published - Jan 19 2007
Externally published	Yes

Keywords

Akt/GSK-3β
Cardiac stem cells
Mesenchymal cells
Proliferation
Survival

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2006.11.096

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title = "Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling",

abstract = "Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardiomyocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3β may be crucial modulators for hCSC maintenance in human heart.",

keywords = "Akt/GSK-3β, Cardiac stem cells, Mesenchymal cells, Proliferation, Survival",

author = "Kento Tateishi and Eishi Ashihara and Shoken Honsho and Naofumi Takehara and Tetsuya Nomura and Tomosaburo Takahashi and Tomomi Ueyama and Masaaki Yamagishi and Hitoshi Yaku and Hiroaki Matsubara and Hidemasa Oh",

note = "Funding Information: We thank Y. Yoshida, A. Kosugi, and M. Nishikawa for technical assistance. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Grants-in-Aid from the Ministry of Health, Labor, and Welfare of Japan.",

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doi = "10.1016/j.bbrc.2006.11.096",

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AU - Tateishi, Kento

AU - Ashihara, Eishi

AU - Honsho, Shoken

AU - Takehara, Naofumi

AU - Nomura, Tetsuya

AU - Takahashi, Tomosaburo

AU - Ueyama, Tomomi

AU - Yamagishi, Masaaki

AU - Yaku, Hitoshi

AU - Matsubara, Hiroaki

AU - Oh, Hidemasa

N1 - Funding Information: We thank Y. Yoshida, A. Kosugi, and M. Nishikawa for technical assistance. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by Grants-in-Aid from the Ministry of Health, Labor, and Welfare of Japan.

PY - 2007/1/19

Y1 - 2007/1/19

N2 - Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardiomyocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3β may be crucial modulators for hCSC maintenance in human heart.

AB - Recent evidence suggested that human cardiac stem cells (hCSCs) may have the clinical application for cardiac repair; however, their characteristics and the regulatory mechanisms of their growth have not been fully investigated. Here, we show the novel property of hCSCs with respect to their origin and tissue distribution in human heart, and demonstrate the signaling pathway that regulates their growth and survival. Telomerase-active hCSCs were predominantly present in the right atrium and outflow tract of the heart (infant > adult) and had a mesenchymal cell-like phenotype. These hCSCs expressed the embryonic stem cell markers and differentiated into cardiomyocytes to support cardiac function when transplanted them into ischemic myocardium. Inhibition of Akt pathway impaired the hCSC proliferation and induced apoptosis, whereas inhibition of glycogen synthase kinase-3 (GSK-3) enhanced their growth and survival. We conclude that hCSCs exhibit mesenchymal features and that Akt/GSK-3β may be crucial modulators for hCSC maintenance in human heart.

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KW - Proliferation

KW - Survival

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Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3β signaling

Abstract

Keywords

ASJC Scopus subject areas

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