TY - JOUR
T1 - Development of a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells
AU - Wei, Heng
AU - Wang, Chen
AU - Guo, Rui
AU - Takahashi, Ken
AU - Naruse, Keiji
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research (S) , No. 26220203 and the Fund for the Promotion of Joint International Research ( Fostering Joint International Research ), 17KK0168 .
Publisher Copyright:
© 2019 The Authors
PY - 2019/12/10
Y1 - 2019/12/10
N2 - Ischemic heart disease remains the largest cause of death worldwide. Accordingly, many researchers have sought curative options, often using laboratory animal models such as rodents. However, the physiology of the human heart differs significantly from that of the rodent heart. In this study, we developed a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CMs). After optimizing the conditions of ischemia, including the concentration of oxygen and duration of application, we evaluated the consequent damage to hiPS-CMs. Notably, exposure to 2% oxygen, 0 mg/ml glucose, and 0% fetal bovine serum increased the percentage of nuclei stained with propidium iodide, an indicator of membrane damage, and decreased cellular viability. These conditions also decreased the contractility of hiPS-CMs. Furthermore, ischemic conditioning increased the mRNA expression of IL-8, consistent with observed conditions in the in vivo heart. Taken together, these findings suggest that our hiPS-CM-based model can provide a useful platform for human ischemic heart disease research.
AB - Ischemic heart disease remains the largest cause of death worldwide. Accordingly, many researchers have sought curative options, often using laboratory animal models such as rodents. However, the physiology of the human heart differs significantly from that of the rodent heart. In this study, we developed a model of ischemic heart disease using cardiomyocytes differentiated from human induced pluripotent stem cells (hiPS-CMs). After optimizing the conditions of ischemia, including the concentration of oxygen and duration of application, we evaluated the consequent damage to hiPS-CMs. Notably, exposure to 2% oxygen, 0 mg/ml glucose, and 0% fetal bovine serum increased the percentage of nuclei stained with propidium iodide, an indicator of membrane damage, and decreased cellular viability. These conditions also decreased the contractility of hiPS-CMs. Furthermore, ischemic conditioning increased the mRNA expression of IL-8, consistent with observed conditions in the in vivo heart. Taken together, these findings suggest that our hiPS-CM-based model can provide a useful platform for human ischemic heart disease research.
KW - Cardiomyocytes
KW - Human induced pluripotent stem cells
KW - Ischemic heart disease
KW - Myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=85073508811&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073508811&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2019.09.119
DO - 10.1016/j.bbrc.2019.09.119
M3 - Article
C2 - 31623826
AN - SCOPUS:85073508811
VL - 520
SP - 600
EP - 605
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -
