期刊
STEM CELL REVIEWS AND REPORTS
卷 11, 期 4, 页码 560-569出版社
SPRINGER
DOI: 10.1007/s12015-014-9564-6
关键词
Human iPS cells; Cardiac differentiation; WNT signaling; BMP signaling; Lactate enrichment; Disease modeling
资金
- Deutsche Forschungsgemeinschaft DFG [ED79/1-2]
- German Ministry of Education and Research, BMBF [01 GN 0813]
- StemCellFactory project - European Union
- German federal state North Rhine-Westphalia (NRW)
- 'StemCellFactory' projects (North Rhine Westphalian Programme for Regional Competitiveness and Employment (Bio.NRW)
- North Rhine Westphalian Ministry of Innovation, Science and Research Programme Translational Stem Cell Research PtJ-Az. [z1403ts007e]
- [PtJ-Az.: z0911bt027i]
Various strategies have been published enabling cardiomyocyte differentiation of human induced pluripotent stem (iPS) cells. However the complex nature of signaling pathways involved as well as line-to-line variability compromises the application of a particular protocol to robustly obtain cardiomyocytes from multiple iPS lines. Hence it is necessary to identify optimized protocols with alternative combinations of specific growth factors and small molecules to enhance the robustness of cardiac differentiation. Here we focus on systematic modulation of BMP and WNT signaling to enhance cardiac differentiation. Moreover, we improve the efficacy of cardiac differentiation by enrichment via lactate. Using our protocol we show efficient derivation of cardiomyocytes from multiple human iPS lines. In particular we demonstrate cardiomyocyte differentiation within 15 days with an efficiency of up to 95 % as judged by flow cytometry staining against cardiac troponin T. Cardiomyocytes derived were functionally validated by alpha-actinin staining, transmission electron microscopy as well as electrophysiological analysis. We expect our protocol to provide a robust basis for scale-up production of functional iPS cell-derived cardiomyocytes that can be used for cell replacement therapy and disease modeling.
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