title: Icariin induces mouse embryonic stem cell differentiation into beating functional cardiomyocytes.
abstract: Icariin, the primary active component of Epimedium extracts, has recently been shown to induce cardiomyocyte differentiation of murine embryonic stem (mES) cells in vitro. However, as these cardiomyocytes were not functionally characterized, the potential application of icariin-induced cardiomyocytes in clinical practice remains unclear. Therefore, in this study, we characterized the structure and function of icariin-induced cardiomyocytes to evaluate their potential application in transplantation for cardiac failure treatment. mES cells were cultured as embryoid bodies (EBs) via the direct suspension method in the presence of icariin. The protein expression profiles and ultrastructural characteristics of mES cell-derived cardiomyocytes were then characterized by immunofluorescence and transmission electron microscopy, respectively. In addition, the expression of cardiac-specific and calcium handling genes was detected by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cardiomyocytes induced by icariin treatment expressed the cardiac-specific proteins myosin light chain-1v (MLC1v), atrial natriuretic polypeptide (ANP), and cardiac troponin I (cTnI). Furthermore, these cells appeared to possess myofibrils organized into mature sarcomeres that had formed A and I bands. In addition, icariin treatment upregulated the mRNA levels of MLC1v, ANP, cTnI, calsequestrin (CSQ), and sodium-calcium exchanger (NCX) in these cells. Icariin induces the differentiation of mES cells into beating cardiomyocytes with normal structure and function. Therefore, these cells may have promising applications in cardiac cell therapy or tissue engineering.
authors.affiliation: Department of Histology and Embryology, Harbin Medical University, Nangang District, Harbin, Heilongjiang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Xiuwei
authors.initials: X
authors.lastname: Sun
authors.forename: Xiudong
authors.initials: X
authors.lastname: Jin
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunling
authors.initials: C
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Lianhong
authors.initials: L
authors.lastname: Jin
authors.forename: Huiwen
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D020869:Gene Expression Profiling; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D018994:Myosin Light Chains / Q000235:genetics; D014158:Transcription, Genetic; D019210:Troponin I / Q000235:genetics
chemical_list: D005419:Flavonoids; D018994:Myosin Light Chains; D019210:Troponin I; D009320:Atrial Natriuretic Factor; C056599:icariin