Cyclosporin-A potently induces highly cardiogenic progenitors from embryonic stem cells.
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.
Yan
Peishi
P
Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Nagasawa
Atsushi
A
Uosaki
Hideki
H
Sugimoto
Akihiro
A
Yamamizu
Kohei
K
Teranishi
Mizue
M
Matsuda
Hiroyuki
H
Matsuoka
Satoshi
S
Ikeda
Tadashi
T
Komeda
Masashi
M
Sakata
Ryuzo
R
Yamashita
Jun K
JK
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine