Haraguchi Yuji
   Department   Research Institutes and Facilities, Research Institutes and Facilities
   Position   Associate Professor (Fixed Term)
Article types Original article
Language English
Peer review Peer reviewed
Title Creation of mouse embryonic stem cell-derived cardiac cell sheets.
Journal Formal name:Biomaterials
ISSN code:(1878-5905)0142-9612(Linking)
Domestic / ForeginForegin
Publisher Elsevier
Volume, Issue, Page 32(30),pp.7355-62
Author and coauthor MATSUURA Katsuhisa†, MASUDA Shinako, HARAGUCHI Yuji, YASUDA Noriko, SHIMIZU Tatsuya, HAGIWARA Nobuhisa, ZANDSTRA Peter W., OKANO Teruo*
Publication date 2011/10
Summary Research on heart tissue engineering is an exciting and promising area. Although we previously developed bioengineered myocardium using cell sheet-based tissue engineering technologies, the issue of appropriate cell sources remained unresolved. In the present study, we created cell sheets of mouse embryonic stem (ES) cell-derived cardiomyocytes after expansion in three-dimensional stirred suspension cultures. Serial treatment of the suspension cultures with noggin and granulocyte colony-stimulating factor significantly increased the number of cardiomyocytes by more than fourfold compared with untreated cultures. After drug selection for ES cells expressing the neomycin-resistance gene under the control of the α-myosin heavy chain promoter, almost all of the cells showed spontaneous beating and expressed several cardiac contractive proteins in a fine striated pattern. When ES-derived cardiomyocytes alone were seeded onto temperature-responsive culture dishes, cell sheets were not created, whereas cocultures with cardiac fibroblasts promoted cell sheet formation. The cardiomyocytes in the cell sheets beat spontaneously and synchronously, and expressed connexin 43 at the edge of adjacent cardiomyocytes. Furthermore, when the extracellular action potential was recorded, unidirectional action potential propagation was observed. The present findings suggest that stirred suspension cultures with appropriate growth factors are capable of producing cardiomyocytes effectively and easily, and that ES-derived cardiac cell sheets may be a promising tool for the development of bioengineered myocardium.
DOI 10.1016/j.biomaterials.2011.05.042
PMID 21807408