Small molecule cardiogenol C upregulates cardiac markers and induces cardiac functional properties in lineage-committed progenitor cells.
OBJECTIVE
Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules.


METHODS
Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays.


RESULTS
Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies.


CONCLUSIONS
CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.
Center for Physiology and Pharmacology, Department of Neurophysiology and -Pharmacology, Medical University of Vienna, Vienna, Austria.
Agnes K
AK
Mike
Xaver
X
Koenig
Moumita
M
Koley
Philipp
P
Heher
Gerald
G
Wahl
Lena
L
Rubi
Michael
M
Schnürch
Marko D
MD
Mihovilovic
Georg
G
Weitzer
Karlheinz
K
Hilber
D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000187:drug effects*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051379:Mice; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013234:Stem Cells; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D000814:Aniline Compounds; D015415:Biomarkers; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D011743:Pyrimidines; D054852:Small Molecule Libraries; D014157:Transcription Factors; C484397:cardiogenol C; D009320:Atrial Natriuretic Factor