ハラグチ ユウジ   Haraguchi Yuji
  原口 裕次
   所属   研究施設 研究施設
   職種   特任講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Creation of mouse embryonic stem cell-derived cardiac cell sheets.
掲載誌名 正式名:Biomaterials
略  称:Biomaterials
ISSNコード:(1878-5905)0142-9612(Linking)
掲載区分国外
出版社 Elsevier
巻・号・頁 32(30),7355-62頁
著者・共著者 MATSUURA Katsuhisa†, MASUDA Shinako, HARAGUCHI Yuji, YASUDA Noriko, SHIMIZU Tatsuya, HAGIWARA Nobuhisa, ZANDSTRA Peter W., OKANO Teruo*
発行年月 2011/10
概要 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