Salvianolic acid B-vitamin C synergy in cardiac differentiation from embryonic stem cells.
Inefficient cardiomyocyte differentiation limits the therapeutic use of embryonic stem (ES) cell-derived cardiomyocytes. While large collections of proprietary chemicals had been screened to improve ES cell differentiation into cardiomyocytes, the natural product library remained unexplored. Using a mouse ES cell line transfected with a cardiomyocyte-specific alpha-myosin heavy chain promoter-driven enhanced green fluorescent protein (EGFP) reporter, we screened 24 natural products with known cardioprotective actions. Salvianolic acid B (saB), while produced minimal effect on its own, concentration-dependently synergized with vitamin C in inducing cardiomyocyte differentiation, as demonstrated by an increase in EGFP(+) cells, beating area in embryoid bodies, and expression of cardiomyocyte maturity markers. This synergy is specific to cardiomyocyte differentiation, and is involved with collagen synthesis. The present study demonstrates the saB-vitamin C synergy in inducing ES cell differentiation into matured and functional cardiomyocytes, and this may lead to a practicable cocktail approach to generate ES cell-derived cardiomyocytes for cardiac stem cell therapy.
Chan
Sunny Sun-Kin
SS
Institute of Clinical Medicine and Research Center for Clinical Medicine, National Cheng Kung University & Hospital, Tainan, Taiwan, ROC.
Chen
Jyh-Hong
JH
Hwang
Shiaw-Min
SM
Wang
I-Ju
IJ
Li
Hui-Jing
HJ
Lee
Richard T
RT
Hsieh
Patrick C H
PC
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001572:Benzofurans / Q000302:isolation & purification / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D032383:Myocytes, Cardiac / Q000502:physiology*; D014815:Vitamins / Q000494:pharmacology*; D053630:Depsides
D001205:Ascorbic Acid; D001572:Benzofurans; D002316:Cardiotonic Agents; D003094:Collagen; D014815:Vitamins; C076944:salvianolic acid B; D053630:Depsides