The promotion of cardiogenic differentiation of hMSCs by targeting epidermal growth factor receptor using microRNA-133a.
Human bone marrow-derived mesenchymal stem cells (hMSCs) are an attractive candidate for cell therapy in heart disease. Low survival and incomplete electromechanical integration between resident cardiomyocytes and transplanted hMSCs remain unsolved. In order for an infarcted heart to tolerate transplantation, differentiation capacity in stem cells must be reinforced. In this study, we found that compound 56, an epidermal growth factor receptor (EGFR) inhibitor, promotes cardiogenic differentiation of hMSCs and the transplantation of hMSCs treated with compound 56 resulted in enhancement of heart functions. Furthermore, hMSCs transfected with microRNA-133a (miR-133a), which targets EGFR, were observed to express cardiac-specific markers. We also discovered that luciferase activity is exclusively decreased by targeting EGFR in hMSCs transfected with miR-133a mimic. These results suggest that EGFR plays a key role in the regulation of cardiogenic differentiation in hMSCs.
Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
Se-Yeon
SY
Lee
Onju
O
Ham
Min-Ji
MJ
Cha
Byeong-Wook
BW
Song
Eunmi
E
Choi
Il-Kwon
IK
Kim
Woochul
W
Chang
Soyeon
S
Lim
Chang Youn
CY
Lee
Jun-Hee
JH
Park
Jiyun
J
Lee
Yoonjin
Y
Bae
Hyang-Hee
HH
Seo
Eunhyun
E
Choi
Yangsoo
Y
Jang
Ki-Chul
KC
Hwang
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002454:Cell Differentiation / Q000187:drug effects; D006224:Cricetinae; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation
C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors