Human cardiac stem cells exhibit mesenchymal features and are maintained through Akt/GSK-3beta signaling.
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-3beta may be crucial modulators for hCSC maintenance in human heart.
Tateishi
Kento
K
Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan.
Ashihara
Eishi
E
Honsho
Shoken
S
Takehara
Naofumi
N
Nomura
Tetsuya
T
Takahashi
Tomosaburo
T
Ueyama
Tomomi
T
Yamagishi
Masaaki
M
Yaku
Hitoshi
H
Matsubara
Hiroaki
H
Oh
Hidemasa
H
D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051058:Oncogene Protein v-akt; D038362:Glycogen Synthase Kinase 3