[Cell Reports] A Small Molecule that Promotes Cardiac Differentiation of Human Pluripotent Stem Cells under Defined, Cytokine- and Xeno-free Conditions
26 October 2012
[Cell Reports] 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. The Norio Nakatsuji and Motonari Uesugi labs, and their colleagues have demonstrated that 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. [
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These findings have received nationwide media coverage in Japan.
Publication information
A Small Molecule that Promotes Cardiac Differentiation of Human Pluripotent Stem Cells under Defined, Cytokine- and Xeno-free Conditions
Itsunari Minami, Kohei Yamada, Tomomi G. Otsuji, Takuya Yamamoto, Yan Shen, Shinya Otsuka, Shin Kadota, Nobuhiro Morone, Maneesha Barve, Yasuyuki Asai, Tatyana Tenkova-Heuser, John E. Heuser, Motonari Uesugi*, Kazuhiro Aiba*, Norio Nakatsuji
Cell Reports | Published online 25 October 2012 | DOI: 10.1016/j.celrep.2012.09.015