title: Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells.
abstract: Though cardiac progenitor cells should be a suitable material for cardiac regeneration, efficient ways to induce cardiac progenitors from embryonic stem (ES) cells have not been established. Extending our systematic cardiovascular differentiation method of ES cells, here we show efficient and specific expansion of cardiomyocytes and highly cardiogenic progenitors from ES cells. An immunosuppressant, cyclosporin-A (CSA), showed a novel effect specifically acting on mesoderm cells to drastically increase cardiac progenitors as well as cardiomyocytes by 10-20 times. Approximately 200 cardiomyocytes could be induced from one mouse ES cell using this method. Expanded progenitors successfully integrated into scar tissue of infracted heart as cardiomyocytes after cell transplantation to rat myocardial infarction model. CSA elicited specific induction of cardiac lineage from mesoderm in a novel mesoderm-specific, NFAT independent fashion. This simple but efficient differentiation technology would be extended to induce pluripotent stem (iPS) cells and broadly contribute to cardiac regeneration.
authors.affiliation: Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Peishi
authors.initials: P
authors.lastname: Yan
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagasawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Uosaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sugimoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamamizu
authors.forename: Mizue
authors.initials: M
authors.lastname: Teranishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Masashi
authors.initials: M
authors.lastname: Komeda
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Sakata
authors.forename: Jun K
authors.initials: JK
authors.lastname: Yamashita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006321:Heart / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D051381:Rats; D012038:Regeneration
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine