title: A small molecule that promotes cardiac differentiation of human pluripotent stem cells under defined, cytokine- and xeno-free conditions.
abstract: Human pluripotent stem cells (hPSCs), including embryonic stem cells and induced pluripotent stem cells, are potentially useful in regenerative therapies for heart disease. For medical applications, clinical-grade cardiac cells must be produced from hPSCs in a defined, cost-effective manner. Cell-based screening led to the discovery of KY02111, a small molecule that promotes differentiation of hPSCs to cardiomyocytes. Although the direct target of KY02111 remains unknown, results of the present study suggest that KY02111 promotes differentiation by inhibiting WNT signaling in hPSCs but in a manner that is distinct from that of previously studied WNT inhibitors. Combined use of KY02111 and WNT signaling modulators produced robust cardiac differentiation of hPSCs in a xeno-free, defined medium, devoid of serum and any kind of recombinant cytokines and hormones, such as BMP4, Activin A, or insulin. The methodology has potential as a means for the practical production of human cardiomyocytes for regeneration therapies.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Itsunari
authors.initials: I
authors.lastname: Minami
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamada
authors.forename: Tomomi G
authors.initials: TG
authors.lastname: Otsuji
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Shinya
authors.initials: S
authors.lastname: Otsuka
authors.forename: Shin
authors.initials: S
authors.lastname: Kadota
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Morone
authors.forename: Maneesha
authors.initials: M
authors.lastname: Barve
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Asai
authors.forename: Tatyana
authors.initials: T
authors.lastname: Tenkova-Heuser
authors.forename: John E
authors.initials: JE
authors.lastname: Heuser
authors.forename: Motonari
authors.initials: M
authors.lastname: Uesugi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Aiba
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology*; D057809:HEK293 Cells; D000882:Haplorhini; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology*; D010666:Phenylpropionates / Q000737:chemistry / Q000494:pharmacology*; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D016895:Culture Media, Serum-Free; C580954:KY02111; D010666:Phenylpropionates; D051153:Wnt Proteins